甲状腺乳头状微小癌颈淋巴结转移风险预测模型的建立及前瞻性验证研究
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摘要
第一部分甲状腺乳头状微小癌多灶性与颈淋巴结转移风险的系统综述及荟萃分析
系统检索甲状腺乳头状微小癌的相关研究，对多灶性及颈淋巴结转移进行荟萃分析，并采用Mantel-Haen-szel法进行meta分析，计算总的相对危险度，以系统评价甲状腺乳头状微小癌多灶性与颈淋巴结转移风险的相关性。共14个临床研究3549名患者被纳入meta分析，所有患者均接受了颈淋巴结清扫术。与单灶微小癌相比，多灶者淋巴结转移风险显著增高，合并比值比为1.7，95%可信区间为1.1-2.7。按手术方式进行亚组分析后，研究间异质性显著降低。因而得出结论多灶甲状腺微小癌更易发生颈淋巴结转移，这部分病人可能从预防性颈淋巴结清扫获益。对于临床试验，不同的干预措施是造成异质性的主要原因。
第二部分回顾性分析发现甲状腺乳头状微小癌颈淋巴结转移风险新的独立预测指标：多灶性联合癌灶总直径
通过回顾性分析武汉协和医院2003-2012年所有接受手术治疗的甲状腺恶性肿瘤病例的临床病理特征，找出甲状腺乳头状微小癌颈淋巴结转移风险因素。此研究期间共有1456例甲状腺癌患者在该院接受手术治疗，选取其中初次手术且手术方式为甲状腺全切+中央区淋巴结清扫、术后病理证实为甲状腺乳头状微小癌病例，深入分析其临床病理特征。对于多灶性疾病，将其所有病灶最大径相加作为其癌灶总直径，并将癌灶总直径作为该病例的病理特征纳入分析。结果发现年龄、性别、多灶性、包膜侵犯、局部浸润均是甲状腺乳头状微小癌中央区淋巴结转移的独立危险因素；纳入癌灶总直径这一新的变量后，癌灶总直径大于1的微小癌颈淋巴结转移率明显高于单灶微小癌（60.4%vs.30%, P<0.001）；癌灶总直径<1的多灶微小癌与单灶微小癌颈淋巴结转移风险无显著性差异（37.5%vs.30%, P=0.463）。我们的研究显示多灶性联合癌灶总直径作为甲状腺微小癌危险度的分级指标更有意义；癌灶总直径>1cm的甲状腺微小癌淋巴结转移风险明显增高，我们建议对这部分病人考虑行预防性颈淋巴结清扫。
第三部分统计学方法建立甲状腺微小癌颈淋巴结转移风险预测模型
在甲状腺的临床诊治工作中，已有数个甲状腺癌风险分级和预后评估系统因其简单实用直观易于理解而深受临床医生和患者欢迎。然而尚没有一个简单的评分系统来指导手术方式的选择。我们期望可以建立一个简单易用的评分系统帮助临床医生评估微小癌患者颈淋巴结转移风险，从而选择哪些患者适合常规进行颈淋巴结清扫。通过回顾性分析我院2003-2012年以来所有初次手术且术后常规病理证实为微小癌的病例特点，找出影响颈淋巴结转移相关因素，统计学方法建立模型，以期在术前通过患者一般特征、影像学检查联合术中所见评估患者淋巴结转移风险，帮助术者选择手术方式。基于第二部分的发现，此部分纳入癌灶总直径这一新的临床特征，选择病例年龄、性别、癌灶最大径、癌灶总直径、多灶性共5项术前易评估的因素，通过计算其权重及对模型的贡献值赋予风险得分，纳入最终模型。数学方法评估模型的解释度。该评分系统结果易于解释，有利于临床医生预测评估微小癌患者就诊时发生颈淋巴结转移风险，对颈淋巴结清扫术的选择提供指导。
第四部分甲状腺乳头状微小癌颈淋巴结转移风险预测模型的前瞻性验证研究
我们通过前述回顾性研究建立了甲状腺乳头状微小癌颈淋巴结转移风险的预测模型。为了验证此模型的稳定性及准确度，于2012年12月在武汉协和医院甲状腺乳腺外科开展前瞻性验证研究。对于因甲状腺微小癌就诊于我科的初治患者，根据其临床病理特征评估其发生颈淋巴结转移风险，对于评估为中、高危患者，给予预防性颈淋巴结清扫术，术后记录其临床病理特征，与术前评分比较，结果发现评分越高者，颈淋巴结转移人数比例越高，定量评估系统评估为高危的患者，即得分>6分的患者，90%以上的病例发生了颈淋巴结转移；而对于评估为中危的患者，即得分4-6分的微小癌患者，40%左右的病例发生了颈淋巴结转移，两者间有显著统计学差异。通过前瞻性验证研究，我们发现甲状腺乳头状微小癌颈淋巴结转移风险预测模型可以帮助临床医生术前、术中评估甲状腺微小癌个体发生颈淋巴结转移的风险，以选择最佳手术方式。
Part1Association between multifocality and cervical lymph node metastasis inpapillary thyroid microcarcinoma: a systematic review and meta-analysis
Studies have shown multifocality significantly increases lymph node metastasis risk inpapillary thyroid carcinoma, but the association in microcarcinoma is controversial. This isa systematic review and meta-analysis of the role of multifocality in papillary thyroidmicrocarcinoma. A systematic search was performed in databases to identify all originalarticles employing the association between multifocality and lymph node metastasis amongpapillary thyroid microcarcinomas. Eligible studies were carefully reviewed and analyzed.A meta-analysis of fourteen publications with a total3549papillary thyroidmicrocarcinomas demonstrated that multifocality was significantly associated with LNMrisk with an odds ratio of1.7(95%confidence interval,1.1-2.7). Patinets who havemultifocal papillary thyroid microcarcinoma are at high risk of lymph node metastasis.Total thyroidectomy associated with routine central neck dissection may be the best surgicalapproach.
Part2Risk for cervical lymph node metastasis among papillary thyroidmicrocarcinoma
To identify high-risk papillary thyroid microcarcinoma (PMC) inclined to lymph nodemetastasis (LNM), we conducted this hospital-based retrospective study. Patients whounderwent total thyroidectomy with central neck dissection and had a pathologicaldiagnosis of PMC between2003and2010at Wuhan Union Hospital were included in thisstudy. The frequency of LNM was retrospectively analyzed according to theclinicopathological features. For multifocal lesions, total tumor diameter was calculated asthe sum of the maximal diameter of each lesion. Age, gender, multifocality, capsularinvasion and local infiltration were independent factors that associated with cervical LNMin PMC. The proportion of LNM was similar between multifocal PMCs with total tumordiameter less than or equal to1cm and unifocal tumors with diameter less than or equal to1cm (37.5vs.30%, P=0.463). LNM frequency was56.89%among multifocal PMC withtotal tumor diameter greater than1cm but less than2cm, and64.9%among unifocaltumors with diameter greater than1cm but less than2cm with no significant difference between the two groups (P=0.330). However, LNM frequency was significantly higher inmultifocal PMCs with total tumor diameter greater than1cm than unifocal tumors withdiameter less than or equal to1cm (60.4vs.30%, P<0.001). Our study indicated that it wasmultifocality along with total tumor diameter that significantly affected LNM risk in PMCpatients.
Part3A reliable and easy-to-use scoring system facilitating selection of prophylacticcentral neck dissection among papillary thyroid microcarcinomas based on theretrospective study
Numerous classifications have been developed to determine prognositic factors forpatients with papillary thyroid carcinoma, including the TNM (tumor, node, metastasis)classification by the International Union Against Cancer, the AGES (age, grade, extent, andsize) classification by Mayor’s clinic, and EORTC prognostic index by the EuropeanOrganization for Research and Treatment of Cancer. We conducted this study to providetables that allow thyroid surgeons to easily calculate a thyroid microcarcinoma patient’srisks of cervical lymph node metastasis preoperatively. A combined analysis was carried outof individual patient data from437papillary thyroid microcarcinoma patients whounderwent thyroid surgery for papillary thyroid microcarcinoma during2003-2012inWuhan Union Hospital. A simple scoring system was derived based on5clinical andpathological factors: sex, age, number of tumors, the maximum tumor size, total tumordiameter. The probabilities of developing cervical lymph node metastasis from less than10%to almost100%among groups based on the score. With the scoring system, the urologistcan discuss the different options with the patient to determine the most appropriatetreatment.
Part4A reliable and easy-to-use scoring system facilitating selection of prophylacticcentral neck dissection among papillary thyroid microcarcinomas: a prospective study
We conducted this prospective study to evaluate the above scoring system forpredicting cervical lymph node metastasis among papillary thyroid microcarcinoma. In thisprospecive study, we assessed104patients with papillary thyroid micocarcinoma and todetermine the predictive accuracy of the above scoring system applicable to the study population. With regard to cervical lymph node metastasis, the difference between therespective stages and/or risk groups was highly significant. The probability to developcervical lymph node metastasis among high risk group, namely those scoring more than6was more than90%. However, the probability to develop cervical lymph node metastasisamong middle risk group, namely those scoring more than4but less than6, was around40%. Moreover, among each risk group, the probability to develop cervical lymph nodemetastasis was increased along with increasing score. In conclusion, the scoring system forpredicting cervical lymph node metastasis among papillary thyroid microcarcinoma isreliable and accurate to facilitate thyroid surgeons choosing the most appropriate surgicalprocedure. Moreover, the individual factors such as age, sex, tumor size are easy to obtainand generally available.
系统检索甲状腺乳头状微小癌的相关研究，对多灶性及颈淋巴结转移进行荟萃分析，并采用Mantel-Haen-szel法进行meta分析，计算总的相对危险度，以系统评价甲状腺乳头状微小癌多灶性与颈淋巴结转移风险的相关性。共14个临床研究3549名患者被纳入meta分析，所有患者均接受了颈淋巴结清扫术。与单灶微小癌相比，多灶者淋巴结转移风险显著增高，合并比值比为1.7，95%可信区间为1.1-2.7。按手术方式进行亚组分析后，研究间异质性显著降低。因而得出结论多灶甲状腺微小癌更易发生颈淋巴结转移，这部分病人可能从预防性颈淋巴结清扫获益。对于临床试验，不同的干预措施是造成异质性的主要原因。
第二部分回顾性分析发现甲状腺乳头状微小癌颈淋巴结转移风险新的独立预测指标：多灶性联合癌灶总直径
通过回顾性分析武汉协和医院2003-2012年所有接受手术治疗的甲状腺恶性肿瘤病例的临床病理特征，找出甲状腺乳头状微小癌颈淋巴结转移风险因素。此研究期间共有1456例甲状腺癌患者在该院接受手术治疗，选取其中初次手术且手术方式为甲状腺全切+中央区淋巴结清扫、术后病理证实为甲状腺乳头状微小癌病例，深入分析其临床病理特征。对于多灶性疾病，将其所有病灶最大径相加作为其癌灶总直径，并将癌灶总直径作为该病例的病理特征纳入分析。结果发现年龄、性别、多灶性、包膜侵犯、局部浸润均是甲状腺乳头状微小癌中央区淋巴结转移的独立危险因素；纳入癌灶总直径这一新的变量后，癌灶总直径大于1的微小癌颈淋巴结转移率明显高于单灶微小癌（60.4%vs.30%, P<0.001）；癌灶总直径<1的多灶微小癌与单灶微小癌颈淋巴结转移风险无显著性差异（37.5%vs.30%, P=0.463）。我们的研究显示多灶性联合癌灶总直径作为甲状腺微小癌危险度的分级指标更有意义；癌灶总直径>1cm的甲状腺微小癌淋巴结转移风险明显增高，我们建议对这部分病人考虑行预防性颈淋巴结清扫。
第三部分统计学方法建立甲状腺微小癌颈淋巴结转移风险预测模型
在甲状腺的临床诊治工作中，已有数个甲状腺癌风险分级和预后评估系统因其简单实用直观易于理解而深受临床医生和患者欢迎。然而尚没有一个简单的评分系统来指导手术方式的选择。我们期望可以建立一个简单易用的评分系统帮助临床医生评估微小癌患者颈淋巴结转移风险，从而选择哪些患者适合常规进行颈淋巴结清扫。通过回顾性分析我院2003-2012年以来所有初次手术且术后常规病理证实为微小癌的病例特点，找出影响颈淋巴结转移相关因素，统计学方法建立模型，以期在术前通过患者一般特征、影像学检查联合术中所见评估患者淋巴结转移风险，帮助术者选择手术方式。基于第二部分的发现，此部分纳入癌灶总直径这一新的临床特征，选择病例年龄、性别、癌灶最大径、癌灶总直径、多灶性共5项术前易评估的因素，通过计算其权重及对模型的贡献值赋予风险得分，纳入最终模型。数学方法评估模型的解释度。该评分系统结果易于解释，有利于临床医生预测评估微小癌患者就诊时发生颈淋巴结转移风险，对颈淋巴结清扫术的选择提供指导。
第四部分甲状腺乳头状微小癌颈淋巴结转移风险预测模型的前瞻性验证研究
我们通过前述回顾性研究建立了甲状腺乳头状微小癌颈淋巴结转移风险的预测模型。为了验证此模型的稳定性及准确度，于2012年12月在武汉协和医院甲状腺乳腺外科开展前瞻性验证研究。对于因甲状腺微小癌就诊于我科的初治患者，根据其临床病理特征评估其发生颈淋巴结转移风险，对于评估为中、高危患者，给予预防性颈淋巴结清扫术，术后记录其临床病理特征，与术前评分比较，结果发现评分越高者，颈淋巴结转移人数比例越高，定量评估系统评估为高危的患者，即得分>6分的患者，90%以上的病例发生了颈淋巴结转移；而对于评估为中危的患者，即得分4-6分的微小癌患者，40%左右的病例发生了颈淋巴结转移，两者间有显著统计学差异。通过前瞻性验证研究，我们发现甲状腺乳头状微小癌颈淋巴结转移风险预测模型可以帮助临床医生术前、术中评估甲状腺微小癌个体发生颈淋巴结转移的风险，以选择最佳手术方式。
Part1Association between multifocality and cervical lymph node metastasis inpapillary thyroid microcarcinoma: a systematic review and meta-analysis
Studies have shown multifocality significantly increases lymph node metastasis risk inpapillary thyroid carcinoma, but the association in microcarcinoma is controversial. This isa systematic review and meta-analysis of the role of multifocality in papillary thyroidmicrocarcinoma. A systematic search was performed in databases to identify all originalarticles employing the association between multifocality and lymph node metastasis amongpapillary thyroid microcarcinomas. Eligible studies were carefully reviewed and analyzed.A meta-analysis of fourteen publications with a total3549papillary thyroidmicrocarcinomas demonstrated that multifocality was significantly associated with LNMrisk with an odds ratio of1.7(95%confidence interval,1.1-2.7). Patinets who havemultifocal papillary thyroid microcarcinoma are at high risk of lymph node metastasis.Total thyroidectomy associated with routine central neck dissection may be the best surgicalapproach.
Part2Risk for cervical lymph node metastasis among papillary thyroidmicrocarcinoma
To identify high-risk papillary thyroid microcarcinoma (PMC) inclined to lymph nodemetastasis (LNM), we conducted this hospital-based retrospective study. Patients whounderwent total thyroidectomy with central neck dissection and had a pathologicaldiagnosis of PMC between2003and2010at Wuhan Union Hospital were included in thisstudy. The frequency of LNM was retrospectively analyzed according to theclinicopathological features. For multifocal lesions, total tumor diameter was calculated asthe sum of the maximal diameter of each lesion. Age, gender, multifocality, capsularinvasion and local infiltration were independent factors that associated with cervical LNMin PMC. The proportion of LNM was similar between multifocal PMCs with total tumordiameter less than or equal to1cm and unifocal tumors with diameter less than or equal to1cm (37.5vs.30%, P=0.463). LNM frequency was56.89%among multifocal PMC withtotal tumor diameter greater than1cm but less than2cm, and64.9%among unifocaltumors with diameter greater than1cm but less than2cm with no significant difference between the two groups (P=0.330). However, LNM frequency was significantly higher inmultifocal PMCs with total tumor diameter greater than1cm than unifocal tumors withdiameter less than or equal to1cm (60.4vs.30%, P<0.001). Our study indicated that it wasmultifocality along with total tumor diameter that significantly affected LNM risk in PMCpatients.
Part3A reliable and easy-to-use scoring system facilitating selection of prophylacticcentral neck dissection among papillary thyroid microcarcinomas based on theretrospective study
Numerous classifications have been developed to determine prognositic factors forpatients with papillary thyroid carcinoma, including the TNM (tumor, node, metastasis)classification by the International Union Against Cancer, the AGES (age, grade, extent, andsize) classification by Mayor’s clinic, and EORTC prognostic index by the EuropeanOrganization for Research and Treatment of Cancer. We conducted this study to providetables that allow thyroid surgeons to easily calculate a thyroid microcarcinoma patient’srisks of cervical lymph node metastasis preoperatively. A combined analysis was carried outof individual patient data from437papillary thyroid microcarcinoma patients whounderwent thyroid surgery for papillary thyroid microcarcinoma during2003-2012inWuhan Union Hospital. A simple scoring system was derived based on5clinical andpathological factors: sex, age, number of tumors, the maximum tumor size, total tumordiameter. The probabilities of developing cervical lymph node metastasis from less than10%to almost100%among groups based on the score. With the scoring system, the urologistcan discuss the different options with the patient to determine the most appropriatetreatment.
Part4A reliable and easy-to-use scoring system facilitating selection of prophylacticcentral neck dissection among papillary thyroid microcarcinomas: a prospective study
We conducted this prospective study to evaluate the above scoring system forpredicting cervical lymph node metastasis among papillary thyroid microcarcinoma. In thisprospecive study, we assessed104patients with papillary thyroid micocarcinoma and todetermine the predictive accuracy of the above scoring system applicable to the study population. With regard to cervical lymph node metastasis, the difference between therespective stages and/or risk groups was highly significant. The probability to developcervical lymph node metastasis among high risk group, namely those scoring more than6was more than90%. However, the probability to develop cervical lymph node metastasisamong middle risk group, namely those scoring more than4but less than6, was around40%. Moreover, among each risk group, the probability to develop cervical lymph nodemetastasis was increased along with increasing score. In conclusion, the scoring system forpredicting cervical lymph node metastasis among papillary thyroid microcarcinoma isreliable and accurate to facilitate thyroid surgeons choosing the most appropriate surgicalprocedure. Moreover, the individual factors such as age, sex, tumor size are easy to obtainand generally available.
引文
[1]L.H. Sobin, Histological typing of thyroid tumours. Histopathology16(1990)513.
[2]A. Jemal, F. Bray, M.M. Center, J. Ferlay, E. Ward, D. Forman, Global cancer statistics.CA Cancer J Clin61(2011)69-90.
[3]E.P. Simard, E.M. Ward, R. Siegel, A. Jemal, Cancers with increasing incidence trends inthe United States:1999through2008. CA Cancer J Clin (2012).
[4]R. Siegel, D. Naishadham, A. Jemal, Cancer statistics,2012. CA Cancer J Clin62(2012)10-29.
[5]R. Siegel, D. Naishadham, A. Jemal, Cancer statistics,2013. CA Cancer J Clin63(2013)11-30.
[6]A.Y. Chen, A. Jemal, E.M. Ward, Increasing incidence of differentiated thyroid cancer inthe United States,1988-2005. Cancer115(2009)3801-3807.
[7]L. Davies, H.G. Welch, Increasing incidence of thyroid cancer in the United States,1973-2002. JAMA295(2006)2164-2167.
[8]Y.C. Lim, E.C. Choi, Y.H. Yoon, E.H. Kim, B.S. Koo, Central lymph node metastases inunilateral papillary thyroid microcarcinoma. Br J Surg96(2009)253-257.
[9]G. Mercante, A. Frasoldati, C. Pedroni, D. Formisano, L. Renna, S. Piana, G. Gardini, R.Valcavi, V. Barbieri, Prognostic factors affecting neck lymph node recurrence anddistant metastasis in papillary microcarcinoma of the thyroid: results of a study in445patients. Thyroid19(2009)707-716.
[10]C.P. Lombardi, R. Bellantone, C. De Crea, N.C. Paladino, G. Fadda, M. Salvatori, M.Raffaelli, Papillary thyroid microcarcinoma: extrathyroidal extension, lymph nodemetastases, and risk factors for recurrence in a high prevalence of goiter area. WorldJ Surg34(2010)1214-1221.
[11]Y.H. Xu, H.J. Song, Z.L. Qiu, Q.Y. Luo, Brain metastases with exceptional featuresfrom papillary thyroid carcinoma: report of three cases. Hell J Nucl Med14(2011)56-59.
[12]M. Varsavsky, M. Cortes Berdonces, G. Alonso, A. Garcia Martin, M. Munoz Torres,
[Metastatic adenopathy from a thyroid microcarcinoma: final diagnosis of apresumed paraganglioma]. Endocrinol Nutr58(2011)143-144.
[13]R.A. DeLellis, Pathology and genetics of tumours of endocrine organs, World HealthOrganization,2004.
[14]Y. Ito, T. Uruno, K. Nakano, Y. Takamura, A. Miya, K. Kobayashi, T. Yokozawa, F.Matsuzuka, S. Kuma, K. Kuma, A. Miyauchi, An observation trial without surgicaltreatment in patients with papillary microcarcinoma of the thyroid. Thyroid13(2003)381-387.
[15]M.R. Pelizzo, I.M. Boschin, A. Toniato, A. Piotto, P. Bernante, C. Pagetta, L. Rampin,D. Rubello, Papillary thyroid microcarcinoma (PTMC): prognostic factors,management and outcome in403patients. Eur J Surg Oncol32(2006)1144-1148.
[16]N.O. Kucuk, P. Tari, E. Tokmak, G. Aras, Treatment for microcarcinoma of the thyroid--clinical experience. Clin Nucl Med32(2007)279-281.
[17]L.E. Tisell, B. Nilsson, J. Molne, G. Hansson, M. Fjalling, S. Jansson, U. Wingren,Improved survival of patients with papillary thyroid cancer after surgicalmicrodissection. World J Surg20(1996)854-859.
[18]L. Vini, C. Harmer, Management of thyroid cancer. Lancet Oncol3(2002)407-414.
[19]W.B. Carter, J.B. Tourtelot, J.G. Savell, H. Lilienfeld, New treatments and shiftingparadigms in differentiated thyroid cancer management. Cancer Control18(2011)96-103.
[20]Y.K. So, M.Y. Seo, Y.I. Son, Prophylactic central lymph node dissection for clinicallynode-negative papillary thyroid microcarcinoma: influence on serum thyroglobulinlevel, recurrence rate, and postoperative complications. Surgery151(2012)192-198.
[21]M. Sywak, L. Cornford, P. Roach, P. Stalberg, S. Sidhu, L. Delbridge, Routineipsilateral level VI lymphadenectomy reduces postoperative thyroglobulin levels inpapillary thyroid cancer. Surgery140(2006)1000-1005; discussion1005-1007.
[22]L.A. Burmeister, R.P. du Cret, C.N. Mariash, Local reactions to radioiodine in thetreatment of thyroid cancer. Am J Med90(1991)217-222.
[23]A.W. Wu, M.B. Wang, C.T. Nguyen, Surgical practice patterns in the treatment ofpapillary thyroid microcarcinoma. Arch Otolaryngol Head Neck Surg136(2010)1182-1190.
[24]A. Czarniecka, M. Jarzab, J. Krajewska, E. Chmielik, B. Szczesniak-Klusek, E.Stobiecka, R. Kokot, A. Sacher, S. Poltorak, J. Wloch, Prognostic value of lymphnode metastases of differentiated thyroid cancer (DTC) according to the localadvancement and range of surgical excision. Thyroid Res3(2010)8.
[25]W.T. Shen, L. Ogawa, D. Ruan, I. Suh, Q.Y. Duh, O.H. Clark, Central neck lymph nodedissection for papillary thyroid cancer: the reliability of surgeon judgment inpredicting which patients will benefit. Surgery148(2010)398-403.
[26]Y.S. Lee, K.H. Nam, W.Y. Chung, H.S. Chang, C.S. Park, Postoperative complicationsof thyroid cancer in a single center experience. J Korean Med Sci25(2010)541-545.
[27]Y.K. So, M.Y. Seo, Y.I. Son, Prophylactic central lymph node dissection for clinicallynode-negative papillary thyroid microcarcinoma: Influence on serum thyroglobulinlevel, recurrence rate, and postoperative complications. Surgery (2011).
[28]H.W. Lin, N. Bhattacharyya, Survival impact of treatment options for papillarymicrocarcinoma of the thyroid. Laryngoscope119(2009)1983-1987.
[29]M.A. Moreno, G. Agarwal, R. de Luna, E.R. Siegel, S.I. Sherman, B.S. Edeiken-Monroe, G.L. Clayman, Preoperative lateral neck ultrasonography as a long-termoutcome predictor in papillary thyroid cancer. Arch Otolaryngol Head Neck Surg137(2011)157-162.
[30]I.D. Hay, M.E. Hutchinson, T. Gonzalez-Losada, B. McIver, M.E. Reinalda, C.S. Grant,G.B. Thompson, T.J. Sebo, J.R. Goellner, Papillary thyroid microcarcinoma: a studyof900cases observed in a60-year period. Surgery144(2008)980-987; discussion987-988.
[31]A. Pisanu, I. Reccia, O. Nardello, A. Uccheddu, Risk factors for nodal metastasis andrecurrence among patients with papillary thyroid microcarcinoma: differences inclinical relevance between nonincidental and incidental tumors. World J Surg33(2009)460-468.
[32]F. Vaisman, A. Shaha, S. Fish, R. Tuttle, Initial therapy with either thyroid lobectomy ortotal thyroidectomy without radioactive iodine remnant ablation is associated withvery low rates of structural disease recurrence in properly selected patients withdifferentiated thyroid cancer. Clin Endocrinol (Oxf)(2011).
[33]C.I. Lundgren, P. Hall, P.W. Dickman, J. Zedenius, Clinically significant prognosticfactors for differentiated thyroid carcinoma: a population-based, nested case-controlstudy. Cancer106(2006)524-531.
[34]D.S. Cooper, G.M. Doherty, B.R. Haugen, R.T. Kloos, S.L. Lee, S.J. Mandel, E.L.Mazzaferri, B. McIver, F. Pacini, M. Schlumberger, S.I. Sherman, D.L. Steward,R.M. Tuttle, Revised American Thyroid Association management guidelines forpatients with thyroid nodules and differentiated thyroid cancer. Thyroid19(2009)1167-1214.
[35]C.C. Solorzano, D.M. Carneiro, M. Ramirez, T.M. Lee, G.L. Irvin,3rd, Surgeon-performed ultrasound in the management of thyroid malignancy. Am Surg70(2004)576-580; discussion580-572.
[36]S. Leboulleux, E. Girard, M. Rose, J.P. Travagli, N. Sabbah, B. Caillou, D.M. Hartl, N.Lassau, E. Baudin, M. Schlumberger, Ultrasound criteria of malignancy for cervicallymph nodes in patients followed up for differentiated thyroid cancer. J ClinEndocrinol Metab92(2007)3590-3594.
[37]H.S. Hwang, L.A. Orloff, Efficacy of preoperative neck ultrasound in the detection ofcervical lymph node metastasis from thyroid cancer. Laryngoscope121(2011)487-491.
[38]Y. Ito, C. Tomoda, T. Uruno, Y. Takamura, A. Miya, K. Kobayashi, F. Matsuzuka, K.Kuma, A. Miyauchi, Clinical significance of metastasis to the central compartmentfrom papillary microcarcinoma of the thyroid. World J Surg30(2006)91-99.
[39]J.B. Ogilvie, K.N. Patel, K.S. Heller, Impact of the2009American Thyroid Associationguidelines on the choice of operation for well-differentiated thyroidmicrocarcinomas. Surgery148(2010)1222-1226; discussion1226-1227.
[40]M.P. Connor, D. Wells, C.E. Schmalbach, Variables predictive of bilateral occultpapillary microcarcinoma following total thyroidectomy. Otolaryngol Head NeckSurg144(2011)210-215.
[41]E. Dunki-Jacobs, K. Grannan, S. McDonough, A.M. Engel, Clinically unsuspectedpapillary microcarcinomas of the thyroid: a common finding with favorable biology?Am J Surg203(2012)140-144.
[42]L. Ciuffreda, D. De Martino, N. Bonfitto, R. Scaramuzzi,[Our experience on surgicaltreatment of papillary thyroid microcarcinoma]. G Chir32(2011)41-44.
[43]K. Gulben, U. Berberoglu, O. Celen, H.H. Mersin, Incidental papillary microcarcinomaof the thyroid--factors affecting lymph node metastasis. Langenbecks Arch Surg393(2008)25-29.
[44]S.M. Chow, S.C. Law, J.K. Chan, S.K. Au, S. Yau, W.H. Lau, Papillary microcarcinomaof the thyroid-Prognostic significance of lymph node metastasis and multifocality.Cancer98(2003)31-40.
[45]S.H. Lee, S.S. Lee, S.M. Jin, J.H. Kim, Y.S. Rho, Predictive factors for centralcompartment lymph node metastasis in thyroid papillary microcarcinoma.Laryngoscope118(2008)659-662.
[46]G.C. Yang, V.A. LiVolsi, Z.W. Baloch, Thyroid microcarcinoma: fine-needle aspirationdiagnosis and histologic follow-up. Int J Surg Pathol10(2002)133-139.
[47]N. Neuhold, A. Schultheis, M. Hermann, G. Krotla, O. Koperek, P. Birner, Incidentalpapillary microcarcinoma of the thyroid--further evidence of a very low malignantpotential: a retrospective clinicopathological study with up to30years of follow-up.Ann Surg Oncol18(2011)3430-3436.
[48]B.S. GA Wells, D O'Connell, J Peterson, V Welch, M Losos, P Tugwell, TheNewcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studiesin meta-analyses, in.
[49]T.A. Moo, B. Umunna, M. Kato, D. Butriago, A. Kundel, J.A. Lee, R. Zarnegar, T.J.Fahey,3rd, Ipsilateral versus bilateral central neck lymph node dissection inpapillary thyroid carcinoma. Ann Surg250(2009)403-408.
[50]Y. Xu, J. Wang,[Analysis of lymph node metastasis factors in papillary thyroidmicrocarcinoma]. Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi21(2007)679-682.
[51]Y.L. Zhou, E.L. Gao, W. Zhang, H. Yang, G.L. Guo, X.H. Zhang, O.C. Wang, Factorspredictive of papillary thyroid micro-carcinoma with bilateral involvement andcentral lymph node metastasis: a retrospective study. World J Surg Oncol10(2012)67.
[52]N. Wada, Q.Y. Duh, K. Sugino, H. Iwasaki, K. Kameyama, T. Mimura, K. Ito, H.Takami, Y. Takanashi, Lymph node metastasis from259papillary thyroidmicrocarcinomas: frequency, pattern of occurrence and recurrence, and optimalstrategy for neck dissection. Ann Surg237(2003)399-407.
[53]D. Barbaro, U. Simi, G. Meucci, P. Lapi, P. Orsini, C. Pasquini, Thyroid papillarycancers: microcarcinoma and carcinoma, incidental cancers and non-incidentalcancers-are they different diseases? Clin Endocrinol (Oxf)63(2005)577-581.
[54]Y. Wang, Q.H. Ji, C.P. Huang, Y.X. Zhu, L. Zhang,[Predictive factors for level VIlymph node metastasis in papillary thyroid microcarcinoma]. Zhonghua Wai Ke ZaZhi46(2008)1899-1901.
[55]Y. Shao, X.J. Cai, L. Gao, H. Li, L. Xie,[Clinical factors related to centralcompartment lymph node metastasis in papillary thyroid microcarcinoma: clinicalanalysis of117cases]. Zhonghua Yi Xue Za Zhi89(2009)403-405.
[56]Y.S. Chung, J.Y. Kim, J.S. Bae, B.J. Song, J.S. Kim, H.M. Jeon, S.S. Jeong, E.K. Kim,W.C. Park, Lateral lymph node metastasis in papillary thyroid carcinoma: results oftherapeutic lymph node dissection. Thyroid19(2009)241-246.
[57]Y.K. So, Y.I. Son, S.D. Hong, M.Y. Seo, C.H. Baek, H.S. Jeong, M.K. Chung,Subclinical lymph node metastasis in papillary thyroid microcarcinoma: a study of551resections. Surgery148(2010)526-531.
[58]S.M. Hyun, H.Y. Song, S.Y. Kim, S.Y. Nam, J.L. Roh, M.W. Han, S.H. Choi, Impact ofcombined prophylactic unilateral central neck dissection and hemithyroidectomy inpatients with papillary thyroid microcarcinoma. Ann Surg Oncol19(2012)591-596.
[59]M.K. Chung, J.H. Kim, Y.H. Ko, Y.I. Son, Correlation of lymphatic vessel density andvascular endothelial growth factor with nodal metastasis in papillary thyroidmicrocarcinoma. Head Neck34(2012)846-851.
[60]L. Zhang, W.J. Wei, Q.H. Ji, Y.X. Zhu, Z.Y. Wang, Y. Wang, C.P. Huang, Q. Shen, D.S.Li, Y. Wu, Risk factors for neck nodal metastasis in papillary thyroidmicrocarcinoma: a study of1066patients. J Clin Endocrinol Metab97(2012)1250-1257.
[61]M. Caliskan, J.H. Park, J.S. Jeong, C.R. Lee, S.K. Park, S.W. Kang, J.J. Jeong, W.Y.Chung, C.S. Park, Role of prophylactic ipsilateral central compartment lymph nodedissection in papillary thyroid microcarcinoma. Endocr J59(2012)305-311.
[62]D.I. Kutler, A.D. Crummey, W.I. Kuhel, Routine central compartment lymph nodedissection for patients with papillary thyroid carcinoma. Head Neck34(2012)260-263.
[63]R. Garrel, C. Tripodi, C. Cartier, M. Makeieff, L. Crampette, B. Guerrier, Cervicallymphadenopathies signaling thyroid microcarcinoma. Case study and review of theliterature. Eur Ann Otorhinolaryngol Head Neck Dis128(2011)115-119.
[64]J. Xiang, Y. Wu, D.S. Li, Q. Shen, Z.Y. Wang, T.Q. Sun, Y. An, Q. Guan, New clinicalfeatures of thyroid cancer in eastern China. J Visc Surg147(2010) e53-56.
[65]S. Jacquot-Laperriere, A.P. Timoshenko, J.M. Dumollard, M. Peoc'h, B. Estour, C.Martin, J.M. Prades, Papillary thyroid microcarcinoma: incidence and prognosticfactors. Eur Arch Otorhinolaryngol264(2007)935-939.
[66]N. Besic, G. Pilko, R. Petric, M. Hocevar, J. Zgajnar, Papillary thyroid microcarcinoma:prognostic factors and treatment. J Surg Oncol97(2008)221-225.
[67]J.D. Lin, T.C. Chao, C. Hsueh, S.F. Kuo, High recurrent rate of multicentric papillarythyroid carcinoma. Ann Surg Oncol16(2009)2609-2616.
[68]D. Giordano, P. Gradoni, G. Oretti, E. Molina, T. Ferri, Treatment and prognosticfactors of papillary thyroid microcarcinoma. Clin Otolaryngol35(2010)118-124.
[69]C. Page, A. Biet, P. Boute, P. Cuvelier, V. Strunski,'Aggressive papillary' thyroidmicrocarcinoma. Eur Arch Otorhinolaryngol266(2009)1959-1963.
[70]E. Papini, R. Guglielmi, A. Bianchini, A. Crescenzi, S. Taccogna, F. Nardi, C. Panunzi,R. Rinaldi, V. Toscano, C.M. Pacella, Risk of malignancy in nonpalpable thyroidnodules: predictive value of ultrasound and color-Doppler features. J ClinEndocrinol Metab87(2002)1941-1946.
[1]A. Jemal, F. Bray, M.M. Center, J. Ferlay, E. Ward, D. Forman, Global cancer statistics.CA Cancer J Clin61(2011)69-90.
[2]P. Zhao, M. Dai, W. Chen, N. Li, Cancer trends in China. Jpn J Clin Oncol40(2010)281-285.
[3]C. Lengauer, K.W. Kinzler, B. Vogelstein, Genetic instability in colorectal cancers.Nature386(1997)623-627.
[4]C. Lengauer, K.W. Kinzler, B. Vogelstein, Genetic instabilities in human cancers. Nature396(1998)643-649.
[5]H. Beerman, P.M. Kluin, J. Hermans, C.J. van de Velde, C.J. Cornelisse, Prognosticsignificance of DNA-ploidy in a series of690primary breast cancer patients. Int JCancer45(1990)34-39.
[6]D.P. Cahill, C. Lengauer, J. Yu, G.J. Riggins, J.K. Willson, S.D. Markowitz, K.W.Kinzler, B. Vogelstein, Mutations of mitotic checkpoint genes in human cancers.Nature392(1998)300-303.
[7]I. Bieche, S. Vacher, F. Lallemand, S. Tozlu-Kara, H. Bennani, M. Beuzelin, K. Driouch,E. Rouleau, F. Lerebours, H. Ripoche, G. Cizeron-Clairac, F. Spyratos, R. Lidereau,Expression analysis of mitotic spindle checkpoint genes in breast carcinoma: role ofNDC80/HEC1in early breast tumorigenicity, and a two-gene signature foraneuploidy. Mol Cancer10(2011)23.
[8]B. Yuan, Y. Xu, J.H. Woo, Y. Wang, Y.K. Bae, D.S. Yoon, R.P. Wersto, E. Tully, K.Wilsbach, E. Gabrielson, Increased expression of mitotic checkpoint genes in breastcancer cells with chromosomal instability. Clin Cancer Res12(2006)405-410.
[9]A. Vaclavicek, J.L. Bermejo, B. Wappenschmidt, A. Meindl, C. Sutter, R.K. Schmutzler,M. Kiechle, P. Bugert, B. Burwinkel, C.R. Bartram, K. Hemminki, A. Forsti,Genetic variation in the major mitotic checkpoint genes does not affect familialbreast cancer risk. Breast Cancer Res Treat106(2007)205-213.
[10]Y.L. Lo, J.C. Yu, S.T. Chen, G.C. Hsu, Y.C. Mau, S.L. Yang, P.E. Wu, C.Y. Shen, Breastcancer risk associated with genotypic polymorphism of the mitotic checkpoint genes:a multigenic study on cancer susceptibility. Carcinogenesis28(2007)1079-1086.
[11]A.D. Carlson RW, Anderson BO, et al., NCCN clinical practice guidelins for breastcancer (version1.2012).(2012).
[12]J.C. Barrett, B. Fry, J. Maller, M.J. Daly, Haploview: analysis and visualization of LDand haplotype maps. Bioinformatics21(2005)263-265.
[13]G.H. Hardy, Mendelian proportions in a mixed population.1908. Yale J Biol Med76(2003)79-80.
[14]P. Bruzzi, S.B. Green, D.P. Byar, L.A. Brinton, C. Schairer, Estimating the populationattributable risk for multiple risk factors using case-control data. Am J Epidemiol122(1985)904-914.
[15]J.P. Costantino, M.H. Gail, D. Pee, S. Anderson, C.K. Redmond, J. Benichou, H.S.Wieand, Validation studies for models projecting the risk of invasive and total breastcancer incidence. J Natl Cancer Inst91(1999)1541-1548.
[16]A.J. Sasco, Epidemiology of breast cancer: an environmental disease? APMIS109(2001)321-332.
[17]J.M. Gudas, R.C. Klein, M. Oka, K.H. Cowan, Posttranscriptional regulation of the c-myb proto-oncogene in estrogen receptor-positive breast cancer cells. Clin CancerRes1(1995)235-243.
[18]R.V. Hoch, D.A. Thompson, R.J. Baker, R.J. Weigel, GATA-3is expressed inassociation with estrogen receptor in breast cancer. Int J Cancer84(1999)122-128.
[19]D. Prevot, A.P. Morel, T. Voeltzel, M.C. Rostan, R. Rimokh, J.P. Magaud, L. Corbo,Relationships of the antiproliferative proteins BTG1and BTG2with CAF1, thehuman homolog of a component of the yeast CCR4transcriptional complex:involvement in estrogen receptor alpha signaling pathway. J Biol Chem276(2001)9640-9648.
[20]C. Sotiriou, S.Y. Neo, L.M. McShane, E.L. Korn, P.M. Long, A. Jazaeri, P. Martiat, S.B.Fox, A.L. Harris, E.T. Liu, Breast cancer classification and prognosis based on geneexpression profiles from a population-based study. Proc Natl Acad Sci U S A100(2003)10393-10398.
[21]M.D. Ritchie, L.W. Hahn, N. Roodi, L.R. Bailey, W.D. Dupont, F.F. Parl, J.H. Moore,Multifactor-dimensionality reduction reveals high-order interactions amongestrogen-metabolism genes in sporadic breast cancer. Am J Hum Genet69(2001)138-147.
[22]M.G. FitzGerald, D.J. MacDonald, M. Krainer, I. Hoover, E. O'Neil, H. Unsal, S. Silva-Arrieto, D.M. Finkelstein, P. Beer-Romero, C. Englert, D.C. Sgroi, B.L. Smith, J.W.Younger, J.E. Garber, R.B. Duda, K.A. Mayzel, K.J. Isselbacher, S.H. Friend, D.A.Haber, Germ-line BRCA1mutations in Jewish and non-Jewish women with early-onset breast cancer. N Engl J Med334(1996)143-149.
[23]Y. Hu, G. Wu, M. Rusch, L. Lukes, K.H. Buetow, J. Zhang, K.W. Hunter, Integratedcross-species transcriptional network analysis of metastatic susceptibility. Proc NatlAcad Sci U S A109(2012)3184-3189.
[24]M.A. Hoyt, L. Totis, B.T. Roberts, S. cerevisiae genes required for cell cycle arrest inresponse to loss of microtubule function. Cell66(1991)507-517.
[25]R. Li, A.W. Murray, Feedback control of mitosis in budding yeast. Cell66(1991)519-531.
[26]E. Weiss, M. Winey, The Saccharomyces cerevisiae spindle pole body duplication geneMPS1is part of a mitotic checkpoint. J Cell Biol132(1996)111-123.
[27]S.S. Taylor, E. Ha, F. McKeon, The human homologue of Bub3is required forkinetochore localization of Bub1and a Mad3/Bub1-related protein kinase. J CellBiol142(1998)1-11.
[28]R. Fraschini, E. Formenti, G. Lucchini, S. Piatti, Budding yeast Bub2is localized atspindle pole bodies and activates the mitotic checkpoint via a different pathwayfrom Mad2. J Cell Biol145(1999)979-991.
[29]A. Bloecher, G.M. Venturi, K. Tatchell, Anaphase spindle position is monitored by theBUB2checkpoint. Nat Cell Biol2(2000)556-558.
[30]K.A. Myrie, M.J. Percy, J.N. Azim, C.K. Neeley, E.M. Petty, Mutation and expressionanalysis of human BUB1and BUB1B in aneuploid breast cancer cell lines. CancerLett152(2000)193-199.
[31]A. Langerod, M. Stromberg, K. Chin, V.N. Kristensen, A.L. Borresen-Dale, BUB1infrequently mutated in human breast carcinomas. Hum Mutat22(2003)420.
[32]A. Gemma, Y. Hosoya, M. Seike, K. Uematsu, F. Kurimoto, S. Hibino, A. Yoshimura,M. Shibuya, S. Kudoh, M. Emi, Genomic structure of the human MAD2gene andmutation analysis in human lung and breast cancers. Lung Cancer32(2001)289-295.
[33]K. Mimori, H. Inoue, H. Alder, H. Ueo, Y. Tanaka, M. Mori, Mutation analysis ofhBUB1, human mitotic checkpoint gene in multiple carcinomas. Oncol Rep8(2001)39-42.
[34]A. Gemma, M. Seike, Y. Seike, K. Uematsu, S. Hibino, F. Kurimoto, A. Yoshimura, M.Shibuya, C.C. Harris, S. Kudoh, Somatic mutation of the hBUB1mitotic checkpointgene in primary lung cancer. Genes Chromosomes Cancer29(2000)213-218.
[35]K. Yamaguchi, K. Okami, K. Hibi, S.L. Wehage, J. Jen, D. Sidransky, Mutationanalysis of hBUB1in aneuploid HNSCC and lung cancer cell lines. Cancer Lett139(1999)183-187.
[36]T. Takahashi, N. Haruki, S. Nomoto, A. Masuda, S. Saji, H. Osada, Identification offrequent impairment of the mitotic checkpoint and molecular analysis of the mitoticcheckpoint genes, hsMAD2and p55CDC, in human lung cancers. Oncogene18(1999)4295-4300.
[37]M. Dobles, V. Liberal, M.L. Scott, R. Benezra, P.K. Sorger, Chromosomemissegregation and apoptosis in mice lacking the mitotic checkpoint protein Mad2.Cell101(2000)635-645.
[38]Q. Wang, T. Liu, Y. Fang, S. Xie, X. Huang, R. Mahmood, G. Ramaswamy, K.M.Sakamoto, Z. Darzynkiewicz, M. Xu, W. Dai, BUBR1deficiency results inabnormal megakaryopoiesis. Blood103(2004)1278-1285.
[39]A.A. Burds, A.S. Lutum, P.K. Sorger, Generating chromosome instability through thesimultaneous deletion of Mad2and p53. Proc Natl Acad Sci U S A102(2005)11296-11301.
[40]K. Takagi, Y. Miki, Y. Shibahara, Y. Nakamura, A. Ebata, M. Watanabe, T. Ishida, H.Sasano, T. Suzuki, BUB1immunolocalization in breast carcinoma: its nuclearlocalization as a potent prognostic factor of the patients. Horm Cancer4(2013)92-102.
[41]H. Grabsch, S. Takeno, W.J. Parsons, N. Pomjanski, A. Boecking, H.E. Gabbert, W.Mueller, Overexpression of the mitotic checkpoint genes BUB1, BUBR1, andBUB3in gastric cancer--association with tumour cell proliferation. J Pathol200(2003)16-22.
[42]H. Shigeishi, S. Yoneda, M. Taki, T. Nobumori, K. Ohta, K. Higashikawa, W. Yasui, N.Kamata, Correlation of human Bub1expression with tumor-proliferating activity insalivary gland tumors. Oncol Rep15(2006)933-938.
[43]L. Li, D.B. Xu, X.L. Zhao, T.Y. Hao, Combination analysis of Bub1and Mad2expression in endometrial cancer: act as a prognostic factor in endometrial cancer.Arch Gynecol Obstet (2013).
[44]G. Kumar, E.J. Breen, S. Ranganathan, Identification of ovarian cancer associatedgenes using an integrated approach in a Boolean framework. BMC Syst Biol7(2013)12.
[45]C. Emmanuel, N. Gava, C. Kennedy, R.L. Balleine, R. Sharma, G. Wain, A. Brand, R.Hogg, D. Etemadmoghadam, J. George, M.J. Birrer, C.L. Clarke, G. Chenevix-Trench, D.D. Bowtell, P.R. Harnett, A. deFazio, Comparison of expression profilesin ovarian epithelium in vivo and ovarian cancer identifies novel candidate genesinvolved in disease pathogenesis. PLoS One6(2011) e17617.
[46]D.G. Hebels, D.G. Jennen, M.H. van Herwijnen, E.J. Moonen, M. Pedersen, L.E.Knudsen, J.C. Kleinjans, T.M. de Kok, Whole-genome gene expressionmodifications associated with nitrosamine exposure and micronucleus frequency inhuman blood cells. Mutagenesis26(2011)753-761.
[47]R.H. Chen, J.C. Waters, E.D. Salmon, A.W. Murray, Association of spindle assemblycheckpoint component XMAD2with unattached kinetochores. Science274(1996)242-246.
[48]G.J. Gorbsky, R.H. Chen, A.W. Murray, Microinjection of antibody to Mad2proteininto mammalian cells in mitosis induces premature anaphase. J Cell Biol141(1998)1193-1205.
[49]M.J. Percy, K.A. Myrie, C.K. Neeley, J.N. Azim, S.P. Ethier, E.M. Petty, Expressionand mutational analyses of the human MAD2L1gene in breast cancer cells. GenesChromosomes Cancer29(2000)356-362.
[50]M. Scintu, R. Vitale, M. Prencipe, A.P. Gallo, L. Bonghi, V.M. Valori, E. Maiello, M.Rinaldi, E. Signori, C. Rabitti, M. Carella, B. Dallapiccola, V. Altomare, V.M. Fazio,P. Parrella, Genomic instability and increased expression of BUB1B and MAD2L1genes in ductal breast carcinoma. Cancer Lett254(2007)298-307.
[51]T. Kato, Y. Daigo, M. Aragaki, K. Ishikawa, M. Sato, S. Kondo, M. Kaji,Overexpression of MAD2predicts clinical outcome in primary lung cancer patients.Lung Cancer74(2011)124-131.
[52]L. Yu, S. Liu, W. Guo, B. Zhang, Y. Liang, Q. Feng, Upregulation of Mad2facilitates invivo and in vitro osteosarcoma progression. Oncol Rep28(2012)2170-2176.
[53]Y. Nakano, T. Sumi, M. Morishita, T. Fukuda, H. Nobeyama, H. Yoshida, Y.Matsumoto, T. Yasui, O. Ishiko, Mitotic arrest deficiency2induces carcinogenesisin mucinous ovarian tumors. Oncol Lett3(2012)281-286.
[54]M. Pinto, M.J. Soares, N. Cerveira, R. Henrique, F.R. Ribeiro, J. Oliveira, C. Jeronimo,M.R. Teixeira, Expression changes of the MAD mitotic checkpoint gene family inrenal cell carcinomas characterized by numerical chromosome changes. VirchowsArch450(2007)379-385.
[55]S.E. Ghayad, J.A. Vendrell, I. Bieche, F. Spyratos, C. Dumontet, I. Treilleux, R.Lidereau, P.A. Cohen, Identification of TACC1, NOV, and PTTG1as new candidategenes associated with endocrine therapy resistance in breast cancer. J MolEndocrinol42(2009)87-103.
[56]Y. Chen, P.C. Yeh, J.C. Huang, C.C. Yeh, Y.L. Juang, The spindle checkpoint proteinMAD1regulates the expression of E-cadherin and prevents cell migration. OncolRep27(2012)487-491.
[57]D.T. Lau, A.W. Murray, Mad2and Mad3cooperate to arrest budding yeast in mitosis.Curr Biol22(2012)180-190.
[58]G.A. Barisone, J.S. Yun, E. Diaz, From cerebellar proliferation to tumorigenesis: newinsights into the role of Mad3. Cell Cycle7(2008)423-427.
[59]A. Abrieu, L. Magnaghi-Jaulin, J.A. Kahana, M. Peter, A. Castro, S. Vigneron, T. Lorca,D.W. Cleveland, J.C. Labbe, Mps1is a kinetochore-associated kinase essential forthe vertebrate mitotic checkpoint. Cell106(2001)83-93.
[60]V.M. Stucke, H.H. Sillje, L. Arnaud, E.A. Nigg, Human Mps1kinase is required for thespindle assembly checkpoint but not for centrosome duplication. EMBO J21(2002)1723-1732.
[61]K.G. Hardwick, E. Weiss, F.C. Luca, M. Winey, A.W. Murray, Activation of thebudding yeast spindle assembly checkpoint without mitotic spindle disruption.Science273(1996)953-956.
[62]G. Varetti, C. Guida, S. Santaguida, E. Chiroli, A. Musacchio, Homeostatic control ofmitotic arrest. Mol Cell44(2011)710-720.
[63]R. Chila, C. Celenza, M. Lupi, G. Damia, L. Carrassa, Chk1-Mad2interaction: Acrosslink between the DNA damage checkpoint and the mitotic spindle checkpoint.Cell Cycle12(2013)1083-1090.
[64]L. Carrassa, Y. Sanchez, E. Erba, G. Damia, U2OS cells lacking Chk1undergo aberrantmitosis and fail to activate the spindle checkpoint. J Cell Mol Med13(2009)1565-1576.
[65]H. Yan, S. Zhu, C. Song, N. Liu, J. Kang, Bone morphogenetic protein (BMP)signaling regulates mitotic checkpoint protein levels in human breast cancer cells.Cell Signal24(2012)961-968.
[66]P. Vernole, M.H. Neale, D. Barcaroli, E. Munarriz, R.A. Knight, R. Tomasini, T.W.Mak, G. Melino, V. De Laurenzi, TAp73alpha binds the kinetochore proteins Bub1and Bub3resulting in polyploidy. Cell Cycle8(2009)421-429.
[67]S. Bhattacharjya, S. Nath, J. Ghose, G.P. Maiti, N. Biswas, S. Bandyopadhyay, C.K.Panda, N.P. Bhattacharyya, S. Roychoudhury, miR-125b promotes cell death bytargeting spindle assembly checkpoint gene MAD1and modulating mitoticprogression. Cell Death Differ20(2013)430-442.
[2]A. Jemal, F. Bray, M.M. Center, J. Ferlay, E. Ward, D. Forman, Global cancer statistics.CA Cancer J Clin61(2011)69-90.
[3]E.P. Simard, E.M. Ward, R. Siegel, A. Jemal, Cancers with increasing incidence trends inthe United States:1999through2008. CA Cancer J Clin (2012).
[4]R. Siegel, D. Naishadham, A. Jemal, Cancer statistics,2012. CA Cancer J Clin62(2012)10-29.
[5]R. Siegel, D. Naishadham, A. Jemal, Cancer statistics,2013. CA Cancer J Clin63(2013)11-30.
[6]A.Y. Chen, A. Jemal, E.M. Ward, Increasing incidence of differentiated thyroid cancer inthe United States,1988-2005. Cancer115(2009)3801-3807.
[7]L. Davies, H.G. Welch, Increasing incidence of thyroid cancer in the United States,1973-2002. JAMA295(2006)2164-2167.
[8]Y.C. Lim, E.C. Choi, Y.H. Yoon, E.H. Kim, B.S. Koo, Central lymph node metastases inunilateral papillary thyroid microcarcinoma. Br J Surg96(2009)253-257.
[9]G. Mercante, A. Frasoldati, C. Pedroni, D. Formisano, L. Renna, S. Piana, G. Gardini, R.Valcavi, V. Barbieri, Prognostic factors affecting neck lymph node recurrence anddistant metastasis in papillary microcarcinoma of the thyroid: results of a study in445patients. Thyroid19(2009)707-716.
[10]C.P. Lombardi, R. Bellantone, C. De Crea, N.C. Paladino, G. Fadda, M. Salvatori, M.Raffaelli, Papillary thyroid microcarcinoma: extrathyroidal extension, lymph nodemetastases, and risk factors for recurrence in a high prevalence of goiter area. WorldJ Surg34(2010)1214-1221.
[11]Y.H. Xu, H.J. Song, Z.L. Qiu, Q.Y. Luo, Brain metastases with exceptional featuresfrom papillary thyroid carcinoma: report of three cases. Hell J Nucl Med14(2011)56-59.
[12]M. Varsavsky, M. Cortes Berdonces, G. Alonso, A. Garcia Martin, M. Munoz Torres,
[Metastatic adenopathy from a thyroid microcarcinoma: final diagnosis of apresumed paraganglioma]. Endocrinol Nutr58(2011)143-144.
[13]R.A. DeLellis, Pathology and genetics of tumours of endocrine organs, World HealthOrganization,2004.
[14]Y. Ito, T. Uruno, K. Nakano, Y. Takamura, A. Miya, K. Kobayashi, T. Yokozawa, F.Matsuzuka, S. Kuma, K. Kuma, A. Miyauchi, An observation trial without surgicaltreatment in patients with papillary microcarcinoma of the thyroid. Thyroid13(2003)381-387.
[15]M.R. Pelizzo, I.M. Boschin, A. Toniato, A. Piotto, P. Bernante, C. Pagetta, L. Rampin,D. Rubello, Papillary thyroid microcarcinoma (PTMC): prognostic factors,management and outcome in403patients. Eur J Surg Oncol32(2006)1144-1148.
[16]N.O. Kucuk, P. Tari, E. Tokmak, G. Aras, Treatment for microcarcinoma of the thyroid--clinical experience. Clin Nucl Med32(2007)279-281.
[17]L.E. Tisell, B. Nilsson, J. Molne, G. Hansson, M. Fjalling, S. Jansson, U. Wingren,Improved survival of patients with papillary thyroid cancer after surgicalmicrodissection. World J Surg20(1996)854-859.
[18]L. Vini, C. Harmer, Management of thyroid cancer. Lancet Oncol3(2002)407-414.
[19]W.B. Carter, J.B. Tourtelot, J.G. Savell, H. Lilienfeld, New treatments and shiftingparadigms in differentiated thyroid cancer management. Cancer Control18(2011)96-103.
[20]Y.K. So, M.Y. Seo, Y.I. Son, Prophylactic central lymph node dissection for clinicallynode-negative papillary thyroid microcarcinoma: influence on serum thyroglobulinlevel, recurrence rate, and postoperative complications. Surgery151(2012)192-198.
[21]M. Sywak, L. Cornford, P. Roach, P. Stalberg, S. Sidhu, L. Delbridge, Routineipsilateral level VI lymphadenectomy reduces postoperative thyroglobulin levels inpapillary thyroid cancer. Surgery140(2006)1000-1005; discussion1005-1007.
[22]L.A. Burmeister, R.P. du Cret, C.N. Mariash, Local reactions to radioiodine in thetreatment of thyroid cancer. Am J Med90(1991)217-222.
[23]A.W. Wu, M.B. Wang, C.T. Nguyen, Surgical practice patterns in the treatment ofpapillary thyroid microcarcinoma. Arch Otolaryngol Head Neck Surg136(2010)1182-1190.
[24]A. Czarniecka, M. Jarzab, J. Krajewska, E. Chmielik, B. Szczesniak-Klusek, E.Stobiecka, R. Kokot, A. Sacher, S. Poltorak, J. Wloch, Prognostic value of lymphnode metastases of differentiated thyroid cancer (DTC) according to the localadvancement and range of surgical excision. Thyroid Res3(2010)8.
[25]W.T. Shen, L. Ogawa, D. Ruan, I. Suh, Q.Y. Duh, O.H. Clark, Central neck lymph nodedissection for papillary thyroid cancer: the reliability of surgeon judgment inpredicting which patients will benefit. Surgery148(2010)398-403.
[26]Y.S. Lee, K.H. Nam, W.Y. Chung, H.S. Chang, C.S. Park, Postoperative complicationsof thyroid cancer in a single center experience. J Korean Med Sci25(2010)541-545.
[27]Y.K. So, M.Y. Seo, Y.I. Son, Prophylactic central lymph node dissection for clinicallynode-negative papillary thyroid microcarcinoma: Influence on serum thyroglobulinlevel, recurrence rate, and postoperative complications. Surgery (2011).
[28]H.W. Lin, N. Bhattacharyya, Survival impact of treatment options for papillarymicrocarcinoma of the thyroid. Laryngoscope119(2009)1983-1987.
[29]M.A. Moreno, G. Agarwal, R. de Luna, E.R. Siegel, S.I. Sherman, B.S. Edeiken-Monroe, G.L. Clayman, Preoperative lateral neck ultrasonography as a long-termoutcome predictor in papillary thyroid cancer. Arch Otolaryngol Head Neck Surg137(2011)157-162.
[30]I.D. Hay, M.E. Hutchinson, T. Gonzalez-Losada, B. McIver, M.E. Reinalda, C.S. Grant,G.B. Thompson, T.J. Sebo, J.R. Goellner, Papillary thyroid microcarcinoma: a studyof900cases observed in a60-year period. Surgery144(2008)980-987; discussion987-988.
[31]A. Pisanu, I. Reccia, O. Nardello, A. Uccheddu, Risk factors for nodal metastasis andrecurrence among patients with papillary thyroid microcarcinoma: differences inclinical relevance between nonincidental and incidental tumors. World J Surg33(2009)460-468.
[32]F. Vaisman, A. Shaha, S. Fish, R. Tuttle, Initial therapy with either thyroid lobectomy ortotal thyroidectomy without radioactive iodine remnant ablation is associated withvery low rates of structural disease recurrence in properly selected patients withdifferentiated thyroid cancer. Clin Endocrinol (Oxf)(2011).
[33]C.I. Lundgren, P. Hall, P.W. Dickman, J. Zedenius, Clinically significant prognosticfactors for differentiated thyroid carcinoma: a population-based, nested case-controlstudy. Cancer106(2006)524-531.
[34]D.S. Cooper, G.M. Doherty, B.R. Haugen, R.T. Kloos, S.L. Lee, S.J. Mandel, E.L.Mazzaferri, B. McIver, F. Pacini, M. Schlumberger, S.I. Sherman, D.L. Steward,R.M. Tuttle, Revised American Thyroid Association management guidelines forpatients with thyroid nodules and differentiated thyroid cancer. Thyroid19(2009)1167-1214.
[35]C.C. Solorzano, D.M. Carneiro, M. Ramirez, T.M. Lee, G.L. Irvin,3rd, Surgeon-performed ultrasound in the management of thyroid malignancy. Am Surg70(2004)576-580; discussion580-572.
[36]S. Leboulleux, E. Girard, M. Rose, J.P. Travagli, N. Sabbah, B. Caillou, D.M. Hartl, N.Lassau, E. Baudin, M. Schlumberger, Ultrasound criteria of malignancy for cervicallymph nodes in patients followed up for differentiated thyroid cancer. J ClinEndocrinol Metab92(2007)3590-3594.
[37]H.S. Hwang, L.A. Orloff, Efficacy of preoperative neck ultrasound in the detection ofcervical lymph node metastasis from thyroid cancer. Laryngoscope121(2011)487-491.
[38]Y. Ito, C. Tomoda, T. Uruno, Y. Takamura, A. Miya, K. Kobayashi, F. Matsuzuka, K.Kuma, A. Miyauchi, Clinical significance of metastasis to the central compartmentfrom papillary microcarcinoma of the thyroid. World J Surg30(2006)91-99.
[39]J.B. Ogilvie, K.N. Patel, K.S. Heller, Impact of the2009American Thyroid Associationguidelines on the choice of operation for well-differentiated thyroidmicrocarcinomas. Surgery148(2010)1222-1226; discussion1226-1227.
[40]M.P. Connor, D. Wells, C.E. Schmalbach, Variables predictive of bilateral occultpapillary microcarcinoma following total thyroidectomy. Otolaryngol Head NeckSurg144(2011)210-215.
[41]E. Dunki-Jacobs, K. Grannan, S. McDonough, A.M. Engel, Clinically unsuspectedpapillary microcarcinomas of the thyroid: a common finding with favorable biology?Am J Surg203(2012)140-144.
[42]L. Ciuffreda, D. De Martino, N. Bonfitto, R. Scaramuzzi,[Our experience on surgicaltreatment of papillary thyroid microcarcinoma]. G Chir32(2011)41-44.
[43]K. Gulben, U. Berberoglu, O. Celen, H.H. Mersin, Incidental papillary microcarcinomaof the thyroid--factors affecting lymph node metastasis. Langenbecks Arch Surg393(2008)25-29.
[44]S.M. Chow, S.C. Law, J.K. Chan, S.K. Au, S. Yau, W.H. Lau, Papillary microcarcinomaof the thyroid-Prognostic significance of lymph node metastasis and multifocality.Cancer98(2003)31-40.
[45]S.H. Lee, S.S. Lee, S.M. Jin, J.H. Kim, Y.S. Rho, Predictive factors for centralcompartment lymph node metastasis in thyroid papillary microcarcinoma.Laryngoscope118(2008)659-662.
[46]G.C. Yang, V.A. LiVolsi, Z.W. Baloch, Thyroid microcarcinoma: fine-needle aspirationdiagnosis and histologic follow-up. Int J Surg Pathol10(2002)133-139.
[47]N. Neuhold, A. Schultheis, M. Hermann, G. Krotla, O. Koperek, P. Birner, Incidentalpapillary microcarcinoma of the thyroid--further evidence of a very low malignantpotential: a retrospective clinicopathological study with up to30years of follow-up.Ann Surg Oncol18(2011)3430-3436.
[48]B.S. GA Wells, D O'Connell, J Peterson, V Welch, M Losos, P Tugwell, TheNewcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studiesin meta-analyses, in.
[49]T.A. Moo, B. Umunna, M. Kato, D. Butriago, A. Kundel, J.A. Lee, R. Zarnegar, T.J.Fahey,3rd, Ipsilateral versus bilateral central neck lymph node dissection inpapillary thyroid carcinoma. Ann Surg250(2009)403-408.
[50]Y. Xu, J. Wang,[Analysis of lymph node metastasis factors in papillary thyroidmicrocarcinoma]. Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi21(2007)679-682.
[51]Y.L. Zhou, E.L. Gao, W. Zhang, H. Yang, G.L. Guo, X.H. Zhang, O.C. Wang, Factorspredictive of papillary thyroid micro-carcinoma with bilateral involvement andcentral lymph node metastasis: a retrospective study. World J Surg Oncol10(2012)67.
[52]N. Wada, Q.Y. Duh, K. Sugino, H. Iwasaki, K. Kameyama, T. Mimura, K. Ito, H.Takami, Y. Takanashi, Lymph node metastasis from259papillary thyroidmicrocarcinomas: frequency, pattern of occurrence and recurrence, and optimalstrategy for neck dissection. Ann Surg237(2003)399-407.
[53]D. Barbaro, U. Simi, G. Meucci, P. Lapi, P. Orsini, C. Pasquini, Thyroid papillarycancers: microcarcinoma and carcinoma, incidental cancers and non-incidentalcancers-are they different diseases? Clin Endocrinol (Oxf)63(2005)577-581.
[54]Y. Wang, Q.H. Ji, C.P. Huang, Y.X. Zhu, L. Zhang,[Predictive factors for level VIlymph node metastasis in papillary thyroid microcarcinoma]. Zhonghua Wai Ke ZaZhi46(2008)1899-1901.
[55]Y. Shao, X.J. Cai, L. Gao, H. Li, L. Xie,[Clinical factors related to centralcompartment lymph node metastasis in papillary thyroid microcarcinoma: clinicalanalysis of117cases]. Zhonghua Yi Xue Za Zhi89(2009)403-405.
[56]Y.S. Chung, J.Y. Kim, J.S. Bae, B.J. Song, J.S. Kim, H.M. Jeon, S.S. Jeong, E.K. Kim,W.C. Park, Lateral lymph node metastasis in papillary thyroid carcinoma: results oftherapeutic lymph node dissection. Thyroid19(2009)241-246.
[57]Y.K. So, Y.I. Son, S.D. Hong, M.Y. Seo, C.H. Baek, H.S. Jeong, M.K. Chung,Subclinical lymph node metastasis in papillary thyroid microcarcinoma: a study of551resections. Surgery148(2010)526-531.
[58]S.M. Hyun, H.Y. Song, S.Y. Kim, S.Y. Nam, J.L. Roh, M.W. Han, S.H. Choi, Impact ofcombined prophylactic unilateral central neck dissection and hemithyroidectomy inpatients with papillary thyroid microcarcinoma. Ann Surg Oncol19(2012)591-596.
[59]M.K. Chung, J.H. Kim, Y.H. Ko, Y.I. Son, Correlation of lymphatic vessel density andvascular endothelial growth factor with nodal metastasis in papillary thyroidmicrocarcinoma. Head Neck34(2012)846-851.
[60]L. Zhang, W.J. Wei, Q.H. Ji, Y.X. Zhu, Z.Y. Wang, Y. Wang, C.P. Huang, Q. Shen, D.S.Li, Y. Wu, Risk factors for neck nodal metastasis in papillary thyroidmicrocarcinoma: a study of1066patients. J Clin Endocrinol Metab97(2012)1250-1257.
[61]M. Caliskan, J.H. Park, J.S. Jeong, C.R. Lee, S.K. Park, S.W. Kang, J.J. Jeong, W.Y.Chung, C.S. Park, Role of prophylactic ipsilateral central compartment lymph nodedissection in papillary thyroid microcarcinoma. Endocr J59(2012)305-311.
[62]D.I. Kutler, A.D. Crummey, W.I. Kuhel, Routine central compartment lymph nodedissection for patients with papillary thyroid carcinoma. Head Neck34(2012)260-263.
[63]R. Garrel, C. Tripodi, C. Cartier, M. Makeieff, L. Crampette, B. Guerrier, Cervicallymphadenopathies signaling thyroid microcarcinoma. Case study and review of theliterature. Eur Ann Otorhinolaryngol Head Neck Dis128(2011)115-119.
[64]J. Xiang, Y. Wu, D.S. Li, Q. Shen, Z.Y. Wang, T.Q. Sun, Y. An, Q. Guan, New clinicalfeatures of thyroid cancer in eastern China. J Visc Surg147(2010) e53-56.
[65]S. Jacquot-Laperriere, A.P. Timoshenko, J.M. Dumollard, M. Peoc'h, B. Estour, C.Martin, J.M. Prades, Papillary thyroid microcarcinoma: incidence and prognosticfactors. Eur Arch Otorhinolaryngol264(2007)935-939.
[66]N. Besic, G. Pilko, R. Petric, M. Hocevar, J. Zgajnar, Papillary thyroid microcarcinoma:prognostic factors and treatment. J Surg Oncol97(2008)221-225.
[67]J.D. Lin, T.C. Chao, C. Hsueh, S.F. Kuo, High recurrent rate of multicentric papillarythyroid carcinoma. Ann Surg Oncol16(2009)2609-2616.
[68]D. Giordano, P. Gradoni, G. Oretti, E. Molina, T. Ferri, Treatment and prognosticfactors of papillary thyroid microcarcinoma. Clin Otolaryngol35(2010)118-124.
[69]C. Page, A. Biet, P. Boute, P. Cuvelier, V. Strunski,'Aggressive papillary' thyroidmicrocarcinoma. Eur Arch Otorhinolaryngol266(2009)1959-1963.
[70]E. Papini, R. Guglielmi, A. Bianchini, A. Crescenzi, S. Taccogna, F. Nardi, C. Panunzi,R. Rinaldi, V. Toscano, C.M. Pacella, Risk of malignancy in nonpalpable thyroidnodules: predictive value of ultrasound and color-Doppler features. J ClinEndocrinol Metab87(2002)1941-1946.
[1]A. Jemal, F. Bray, M.M. Center, J. Ferlay, E. Ward, D. Forman, Global cancer statistics.CA Cancer J Clin61(2011)69-90.
[2]P. Zhao, M. Dai, W. Chen, N. Li, Cancer trends in China. Jpn J Clin Oncol40(2010)281-285.
[3]C. Lengauer, K.W. Kinzler, B. Vogelstein, Genetic instability in colorectal cancers.Nature386(1997)623-627.
[4]C. Lengauer, K.W. Kinzler, B. Vogelstein, Genetic instabilities in human cancers. Nature396(1998)643-649.
[5]H. Beerman, P.M. Kluin, J. Hermans, C.J. van de Velde, C.J. Cornelisse, Prognosticsignificance of DNA-ploidy in a series of690primary breast cancer patients. Int JCancer45(1990)34-39.
[6]D.P. Cahill, C. Lengauer, J. Yu, G.J. Riggins, J.K. Willson, S.D. Markowitz, K.W.Kinzler, B. Vogelstein, Mutations of mitotic checkpoint genes in human cancers.Nature392(1998)300-303.
[7]I. Bieche, S. Vacher, F. Lallemand, S. Tozlu-Kara, H. Bennani, M. Beuzelin, K. Driouch,E. Rouleau, F. Lerebours, H. Ripoche, G. Cizeron-Clairac, F. Spyratos, R. Lidereau,Expression analysis of mitotic spindle checkpoint genes in breast carcinoma: role ofNDC80/HEC1in early breast tumorigenicity, and a two-gene signature foraneuploidy. Mol Cancer10(2011)23.
[8]B. Yuan, Y. Xu, J.H. Woo, Y. Wang, Y.K. Bae, D.S. Yoon, R.P. Wersto, E. Tully, K.Wilsbach, E. Gabrielson, Increased expression of mitotic checkpoint genes in breastcancer cells with chromosomal instability. Clin Cancer Res12(2006)405-410.
[9]A. Vaclavicek, J.L. Bermejo, B. Wappenschmidt, A. Meindl, C. Sutter, R.K. Schmutzler,M. Kiechle, P. Bugert, B. Burwinkel, C.R. Bartram, K. Hemminki, A. Forsti,Genetic variation in the major mitotic checkpoint genes does not affect familialbreast cancer risk. Breast Cancer Res Treat106(2007)205-213.
[10]Y.L. Lo, J.C. Yu, S.T. Chen, G.C. Hsu, Y.C. Mau, S.L. Yang, P.E. Wu, C.Y. Shen, Breastcancer risk associated with genotypic polymorphism of the mitotic checkpoint genes:a multigenic study on cancer susceptibility. Carcinogenesis28(2007)1079-1086.
[11]A.D. Carlson RW, Anderson BO, et al., NCCN clinical practice guidelins for breastcancer (version1.2012).(2012).
[12]J.C. Barrett, B. Fry, J. Maller, M.J. Daly, Haploview: analysis and visualization of LDand haplotype maps. Bioinformatics21(2005)263-265.
[13]G.H. Hardy, Mendelian proportions in a mixed population.1908. Yale J Biol Med76(2003)79-80.
[14]P. Bruzzi, S.B. Green, D.P. Byar, L.A. Brinton, C. Schairer, Estimating the populationattributable risk for multiple risk factors using case-control data. Am J Epidemiol122(1985)904-914.
[15]J.P. Costantino, M.H. Gail, D. Pee, S. Anderson, C.K. Redmond, J. Benichou, H.S.Wieand, Validation studies for models projecting the risk of invasive and total breastcancer incidence. J Natl Cancer Inst91(1999)1541-1548.
[16]A.J. Sasco, Epidemiology of breast cancer: an environmental disease? APMIS109(2001)321-332.
[17]J.M. Gudas, R.C. Klein, M. Oka, K.H. Cowan, Posttranscriptional regulation of the c-myb proto-oncogene in estrogen receptor-positive breast cancer cells. Clin CancerRes1(1995)235-243.
[18]R.V. Hoch, D.A. Thompson, R.J. Baker, R.J. Weigel, GATA-3is expressed inassociation with estrogen receptor in breast cancer. Int J Cancer84(1999)122-128.
[19]D. Prevot, A.P. Morel, T. Voeltzel, M.C. Rostan, R. Rimokh, J.P. Magaud, L. Corbo,Relationships of the antiproliferative proteins BTG1and BTG2with CAF1, thehuman homolog of a component of the yeast CCR4transcriptional complex:involvement in estrogen receptor alpha signaling pathway. J Biol Chem276(2001)9640-9648.
[20]C. Sotiriou, S.Y. Neo, L.M. McShane, E.L. Korn, P.M. Long, A. Jazaeri, P. Martiat, S.B.Fox, A.L. Harris, E.T. Liu, Breast cancer classification and prognosis based on geneexpression profiles from a population-based study. Proc Natl Acad Sci U S A100(2003)10393-10398.
[21]M.D. Ritchie, L.W. Hahn, N. Roodi, L.R. Bailey, W.D. Dupont, F.F. Parl, J.H. Moore,Multifactor-dimensionality reduction reveals high-order interactions amongestrogen-metabolism genes in sporadic breast cancer. Am J Hum Genet69(2001)138-147.
[22]M.G. FitzGerald, D.J. MacDonald, M. Krainer, I. Hoover, E. O'Neil, H. Unsal, S. Silva-Arrieto, D.M. Finkelstein, P. Beer-Romero, C. Englert, D.C. Sgroi, B.L. Smith, J.W.Younger, J.E. Garber, R.B. Duda, K.A. Mayzel, K.J. Isselbacher, S.H. Friend, D.A.Haber, Germ-line BRCA1mutations in Jewish and non-Jewish women with early-onset breast cancer. N Engl J Med334(1996)143-149.
[23]Y. Hu, G. Wu, M. Rusch, L. Lukes, K.H. Buetow, J. Zhang, K.W. Hunter, Integratedcross-species transcriptional network analysis of metastatic susceptibility. Proc NatlAcad Sci U S A109(2012)3184-3189.
[24]M.A. Hoyt, L. Totis, B.T. Roberts, S. cerevisiae genes required for cell cycle arrest inresponse to loss of microtubule function. Cell66(1991)507-517.
[25]R. Li, A.W. Murray, Feedback control of mitosis in budding yeast. Cell66(1991)519-531.
[26]E. Weiss, M. Winey, The Saccharomyces cerevisiae spindle pole body duplication geneMPS1is part of a mitotic checkpoint. J Cell Biol132(1996)111-123.
[27]S.S. Taylor, E. Ha, F. McKeon, The human homologue of Bub3is required forkinetochore localization of Bub1and a Mad3/Bub1-related protein kinase. J CellBiol142(1998)1-11.
[28]R. Fraschini, E. Formenti, G. Lucchini, S. Piatti, Budding yeast Bub2is localized atspindle pole bodies and activates the mitotic checkpoint via a different pathwayfrom Mad2. J Cell Biol145(1999)979-991.
[29]A. Bloecher, G.M. Venturi, K. Tatchell, Anaphase spindle position is monitored by theBUB2checkpoint. Nat Cell Biol2(2000)556-558.
[30]K.A. Myrie, M.J. Percy, J.N. Azim, C.K. Neeley, E.M. Petty, Mutation and expressionanalysis of human BUB1and BUB1B in aneuploid breast cancer cell lines. CancerLett152(2000)193-199.
[31]A. Langerod, M. Stromberg, K. Chin, V.N. Kristensen, A.L. Borresen-Dale, BUB1infrequently mutated in human breast carcinomas. Hum Mutat22(2003)420.
[32]A. Gemma, Y. Hosoya, M. Seike, K. Uematsu, F. Kurimoto, S. Hibino, A. Yoshimura,M. Shibuya, S. Kudoh, M. Emi, Genomic structure of the human MAD2gene andmutation analysis in human lung and breast cancers. Lung Cancer32(2001)289-295.
[33]K. Mimori, H. Inoue, H. Alder, H. Ueo, Y. Tanaka, M. Mori, Mutation analysis ofhBUB1, human mitotic checkpoint gene in multiple carcinomas. Oncol Rep8(2001)39-42.
[34]A. Gemma, M. Seike, Y. Seike, K. Uematsu, S. Hibino, F. Kurimoto, A. Yoshimura, M.Shibuya, C.C. Harris, S. Kudoh, Somatic mutation of the hBUB1mitotic checkpointgene in primary lung cancer. Genes Chromosomes Cancer29(2000)213-218.
[35]K. Yamaguchi, K. Okami, K. Hibi, S.L. Wehage, J. Jen, D. Sidransky, Mutationanalysis of hBUB1in aneuploid HNSCC and lung cancer cell lines. Cancer Lett139(1999)183-187.
[36]T. Takahashi, N. Haruki, S. Nomoto, A. Masuda, S. Saji, H. Osada, Identification offrequent impairment of the mitotic checkpoint and molecular analysis of the mitoticcheckpoint genes, hsMAD2and p55CDC, in human lung cancers. Oncogene18(1999)4295-4300.
[37]M. Dobles, V. Liberal, M.L. Scott, R. Benezra, P.K. Sorger, Chromosomemissegregation and apoptosis in mice lacking the mitotic checkpoint protein Mad2.Cell101(2000)635-645.
[38]Q. Wang, T. Liu, Y. Fang, S. Xie, X. Huang, R. Mahmood, G. Ramaswamy, K.M.Sakamoto, Z. Darzynkiewicz, M. Xu, W. Dai, BUBR1deficiency results inabnormal megakaryopoiesis. Blood103(2004)1278-1285.
[39]A.A. Burds, A.S. Lutum, P.K. Sorger, Generating chromosome instability through thesimultaneous deletion of Mad2and p53. Proc Natl Acad Sci U S A102(2005)11296-11301.
[40]K. Takagi, Y. Miki, Y. Shibahara, Y. Nakamura, A. Ebata, M. Watanabe, T. Ishida, H.Sasano, T. Suzuki, BUB1immunolocalization in breast carcinoma: its nuclearlocalization as a potent prognostic factor of the patients. Horm Cancer4(2013)92-102.
[41]H. Grabsch, S. Takeno, W.J. Parsons, N. Pomjanski, A. Boecking, H.E. Gabbert, W.Mueller, Overexpression of the mitotic checkpoint genes BUB1, BUBR1, andBUB3in gastric cancer--association with tumour cell proliferation. J Pathol200(2003)16-22.
[42]H. Shigeishi, S. Yoneda, M. Taki, T. Nobumori, K. Ohta, K. Higashikawa, W. Yasui, N.Kamata, Correlation of human Bub1expression with tumor-proliferating activity insalivary gland tumors. Oncol Rep15(2006)933-938.
[43]L. Li, D.B. Xu, X.L. Zhao, T.Y. Hao, Combination analysis of Bub1and Mad2expression in endometrial cancer: act as a prognostic factor in endometrial cancer.Arch Gynecol Obstet (2013).
[44]G. Kumar, E.J. Breen, S. Ranganathan, Identification of ovarian cancer associatedgenes using an integrated approach in a Boolean framework. BMC Syst Biol7(2013)12.
[45]C. Emmanuel, N. Gava, C. Kennedy, R.L. Balleine, R. Sharma, G. Wain, A. Brand, R.Hogg, D. Etemadmoghadam, J. George, M.J. Birrer, C.L. Clarke, G. Chenevix-Trench, D.D. Bowtell, P.R. Harnett, A. deFazio, Comparison of expression profilesin ovarian epithelium in vivo and ovarian cancer identifies novel candidate genesinvolved in disease pathogenesis. PLoS One6(2011) e17617.
[46]D.G. Hebels, D.G. Jennen, M.H. van Herwijnen, E.J. Moonen, M. Pedersen, L.E.Knudsen, J.C. Kleinjans, T.M. de Kok, Whole-genome gene expressionmodifications associated with nitrosamine exposure and micronucleus frequency inhuman blood cells. Mutagenesis26(2011)753-761.
[47]R.H. Chen, J.C. Waters, E.D. Salmon, A.W. Murray, Association of spindle assemblycheckpoint component XMAD2with unattached kinetochores. Science274(1996)242-246.
[48]G.J. Gorbsky, R.H. Chen, A.W. Murray, Microinjection of antibody to Mad2proteininto mammalian cells in mitosis induces premature anaphase. J Cell Biol141(1998)1193-1205.
[49]M.J. Percy, K.A. Myrie, C.K. Neeley, J.N. Azim, S.P. Ethier, E.M. Petty, Expressionand mutational analyses of the human MAD2L1gene in breast cancer cells. GenesChromosomes Cancer29(2000)356-362.
[50]M. Scintu, R. Vitale, M. Prencipe, A.P. Gallo, L. Bonghi, V.M. Valori, E. Maiello, M.Rinaldi, E. Signori, C. Rabitti, M. Carella, B. Dallapiccola, V. Altomare, V.M. Fazio,P. Parrella, Genomic instability and increased expression of BUB1B and MAD2L1genes in ductal breast carcinoma. Cancer Lett254(2007)298-307.
[51]T. Kato, Y. Daigo, M. Aragaki, K. Ishikawa, M. Sato, S. Kondo, M. Kaji,Overexpression of MAD2predicts clinical outcome in primary lung cancer patients.Lung Cancer74(2011)124-131.
[52]L. Yu, S. Liu, W. Guo, B. Zhang, Y. Liang, Q. Feng, Upregulation of Mad2facilitates invivo and in vitro osteosarcoma progression. Oncol Rep28(2012)2170-2176.
[53]Y. Nakano, T. Sumi, M. Morishita, T. Fukuda, H. Nobeyama, H. Yoshida, Y.Matsumoto, T. Yasui, O. Ishiko, Mitotic arrest deficiency2induces carcinogenesisin mucinous ovarian tumors. Oncol Lett3(2012)281-286.
[54]M. Pinto, M.J. Soares, N. Cerveira, R. Henrique, F.R. Ribeiro, J. Oliveira, C. Jeronimo,M.R. Teixeira, Expression changes of the MAD mitotic checkpoint gene family inrenal cell carcinomas characterized by numerical chromosome changes. VirchowsArch450(2007)379-385.
[55]S.E. Ghayad, J.A. Vendrell, I. Bieche, F. Spyratos, C. Dumontet, I. Treilleux, R.Lidereau, P.A. Cohen, Identification of TACC1, NOV, and PTTG1as new candidategenes associated with endocrine therapy resistance in breast cancer. J MolEndocrinol42(2009)87-103.
[56]Y. Chen, P.C. Yeh, J.C. Huang, C.C. Yeh, Y.L. Juang, The spindle checkpoint proteinMAD1regulates the expression of E-cadherin and prevents cell migration. OncolRep27(2012)487-491.
[57]D.T. Lau, A.W. Murray, Mad2and Mad3cooperate to arrest budding yeast in mitosis.Curr Biol22(2012)180-190.
[58]G.A. Barisone, J.S. Yun, E. Diaz, From cerebellar proliferation to tumorigenesis: newinsights into the role of Mad3. Cell Cycle7(2008)423-427.
[59]A. Abrieu, L. Magnaghi-Jaulin, J.A. Kahana, M. Peter, A. Castro, S. Vigneron, T. Lorca,D.W. Cleveland, J.C. Labbe, Mps1is a kinetochore-associated kinase essential forthe vertebrate mitotic checkpoint. Cell106(2001)83-93.
[60]V.M. Stucke, H.H. Sillje, L. Arnaud, E.A. Nigg, Human Mps1kinase is required for thespindle assembly checkpoint but not for centrosome duplication. EMBO J21(2002)1723-1732.
[61]K.G. Hardwick, E. Weiss, F.C. Luca, M. Winey, A.W. Murray, Activation of thebudding yeast spindle assembly checkpoint without mitotic spindle disruption.Science273(1996)953-956.
[62]G. Varetti, C. Guida, S. Santaguida, E. Chiroli, A. Musacchio, Homeostatic control ofmitotic arrest. Mol Cell44(2011)710-720.
[63]R. Chila, C. Celenza, M. Lupi, G. Damia, L. Carrassa, Chk1-Mad2interaction: Acrosslink between the DNA damage checkpoint and the mitotic spindle checkpoint.Cell Cycle12(2013)1083-1090.
[64]L. Carrassa, Y. Sanchez, E. Erba, G. Damia, U2OS cells lacking Chk1undergo aberrantmitosis and fail to activate the spindle checkpoint. J Cell Mol Med13(2009)1565-1576.
[65]H. Yan, S. Zhu, C. Song, N. Liu, J. Kang, Bone morphogenetic protein (BMP)signaling regulates mitotic checkpoint protein levels in human breast cancer cells.Cell Signal24(2012)961-968.
[66]P. Vernole, M.H. Neale, D. Barcaroli, E. Munarriz, R.A. Knight, R. Tomasini, T.W.Mak, G. Melino, V. De Laurenzi, TAp73alpha binds the kinetochore proteins Bub1and Bub3resulting in polyploidy. Cell Cycle8(2009)421-429.
[67]S. Bhattacharjya, S. Nath, J. Ghose, G.P. Maiti, N. Biswas, S. Bandyopadhyay, C.K.Panda, N.P. Bhattacharyya, S. Roychoudhury, miR-125b promotes cell death bytargeting spindle assembly checkpoint gene MAD1and modulating mitoticprogression. Cell Death Differ20(2013)430-442.