BRAF~(V600E)基因突变与甲状腺微小乳头状癌淋巴结转移的相关性研究
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摘要
目的:探讨甲状腺微小乳头状癌(papillary thyroid microcarcinoma,PTMC)发生淋巴结转移是否与BRAF~(V600E)基因突变相关。方法:回顾性分析行手术治疗的55例甲状腺微小乳头状癌有淋巴结转移(A组)和70例甲状腺微小乳头状癌无淋巴结转移(B组)的患者,用免疫组化对其肿瘤组织及转移性的淋巴结进行BRAF~(V600E)基因突变蛋白检测并通过统计学分析甲状腺微小乳头状癌淋巴结转移与BRAF~(V600E)基因突变的相关性。结果:A组总的BRAF~(V600E)基因突变率(69. 1%)、右侧PTMC(78. 3%)、双侧PTMC的突变率(83. 3%)要分别高于B组(37. 1%、26. 7%、42. 9%)(P值均<0. 05),但强阳性率(23. 6%)和左侧PTMC的突变率(50. 0%)与B组(11. 4%、46. 2%)相比无统计学差异(P值均> 0. 05)。A组组内淋巴结转移灶BRAF~(V600E)基因突变率无论PTMC在左侧(72. 2%)、右侧(92. 0%)或双侧(91. 7%)的阳性率和强阳性率(30. 9%)上与原发灶(50. 0%、78. 3%、83. 3%、23. 6%)均无差异(P> 0. 05),但总的突变率,前者(85. 5%)要高于后者(69. 1%)(P <0. 05)。结论:BRAF~(V600E)突变是导致PTMC早期发生淋巴结转移的重要因素之一,术前或术后通过各种方法测得的BRAF~(V600E)突变阳性预示着淋巴结转移的高风险。
Objective: To study the correlation between papillary thyroid microcarcinoma( PTMC) lymph node metastasis and BRAF~(V600E) mutation. Methods: Retrospectively analyze the BRAF~(V600E) mutant protein of 55 patients of PTMC with lymph node metastasis( group A) and 70 patients of PTMC without lymph node metastasis( group B)through IHC. Then the correlation between PTMC and BRAF~(V600E) mutant was analysed. Results: The gene mutation rates of total BRAFV600E( 69. 1%),right PTMC( 78. 3%) and bilateral PTMC( 83. 3%) of group A were higher than that of group B( 37. 1%,26. 7%,42. 9%)( P < 0. 05). However,the mutation rate of strongly positive( 23. 6%)and mutation rate of left PTMC( 50. 0%) were not statistically significant compared with group B( 11. 4%,46. 2%)( P > 0. 05). In group A,the BRAF~(V600E) mutation rates of left( 7 2. 2 %),right( 9 2. 0 %) and bilateral thyroid( 91. 7%) and strongly positive rate( 30. 9%) in lymph node metastasis lesion had no difference compared with primary lesion( 50. 0%,78. 3%,83. 3%,23. 6%)( P > 0. 05). But,the total mutation rate of the former( 85. 5%)was higher than the later( 69. 1%)( P < 0. 05). Conclusion: BRAF~(V600E) mutation is one of the important factors that lead to early lymph node metastasis in PTMC,and the mutation of BRAF~(V600E) detected by various methods before or after surgery indicates a high risk of lymph node metastasis.
Objective: To study the correlation between papillary thyroid microcarcinoma( PTMC) lymph node metastasis and BRAF~(V600E) mutation. Methods: Retrospectively analyze the BRAF~(V600E) mutant protein of 55 patients of PTMC with lymph node metastasis( group A) and 70 patients of PTMC without lymph node metastasis( group B)through IHC. Then the correlation between PTMC and BRAF~(V600E) mutant was analysed. Results: The gene mutation rates of total BRAFV600E( 69. 1%),right PTMC( 78. 3%) and bilateral PTMC( 83. 3%) of group A were higher than that of group B( 37. 1%,26. 7%,42. 9%)( P < 0. 05). However,the mutation rate of strongly positive( 23. 6%)and mutation rate of left PTMC( 50. 0%) were not statistically significant compared with group B( 11. 4%,46. 2%)( P > 0. 05). In group A,the BRAF~(V600E) mutation rates of left( 7 2. 2 %),right( 9 2. 0 %) and bilateral thyroid( 91. 7%) and strongly positive rate( 30. 9%) in lymph node metastasis lesion had no difference compared with primary lesion( 50. 0%,78. 3%,83. 3%,23. 6%)( P > 0. 05). But,the total mutation rate of the former( 85. 5%)was higher than the later( 69. 1%)( P < 0. 05). Conclusion: BRAF~(V600E) mutation is one of the important factors that lead to early lymph node metastasis in PTMC,and the mutation of BRAF~(V600E) detected by various methods before or after surgery indicates a high risk of lymph node metastasis.
引文
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[11]Dong Liru,Yang Hu,Li Shuang,et al.BRAFV600Emutation and expression of its protein in papillary thyroid carcinoma[J].China Oncology,2017,27(4):251-255.[董丽儒,杨虎,李双,等.甲状腺乳头状癌BRAFV600E基因突变及相关蛋白的表达[J].中国癌症杂志,2017,27(4):251-255.]
[12]Miccoli P,Basolo F.BRAF mutation status in papillary thyroid carcinoma:Significance for surgical strategy[J].Langenbecks Arch Surg,2014,399(2):225-228.
[13]Yip L,Nikiforova MN,Carty SE,et al.Optimizing surgical treatment of papillary thyroid carcinoma associated with BRAF mutation[J].Surgery,2009,146(6):1215-1223.
[14]So YK,Son YI,Hong SD,et al.Subclinical lymph node metastasis in papillary thyroid microcarcinoma:A study of 551 resections[J].Surgery,2010,148(3):526-531.
[15]Howell GM,Nikiforova MN,Carty SE,et al.BRAFV600Emutation independently predicts central compartment lymph node metastasis in patients with papillary thyroid cancer[J].Ann Surg Oncol,2013,20(1):47-52.
[16]Lee JW,Koo BS.The prognostic implication and potential role of BRAF mutation in the decision to perform elective neck dissection for thyroid cancer[J].Gland Surgery,2013,2(4):206-211.
[2]Lee J,Song Y,Soh EY,et al.Central lymph node metastasis is an important prognostic factor in patients with papillary thyroid micro-carcinoma[J].J Korean Med Sci,2014 29(1):48-52.
[3]Wang TS,Goffredo P,Sosa JA,et al.Papillary thyroid micro-carcinoma:An over-treated malignancy[J].World J Surg,2014,38(9):2297-2303.
[4]Yu XM,Wan Y,Sippel RS,et al.Should papillary thyroid microcarcinomas be aggressively treated?An analysis of 18 445 cases[J].Ann Surg,2011,254(4):653-660.
[5]Alzahrani AS,Xing M.Impact of lymph node metastases identified on central neck dissection(CND)on the recurrence of papillary thyroid cancer:Potential role of BRAFV600Emutation in defining CND[J].Endocr Relat Cancer,2013,20(1):13-22.
[6]Cohen Y,Xing M,Mambo E,et al.BRAF mutation in papillary thyroid carcinoma[J].J Natl Cancer Inst,2003,95(8):625-627.
[7]Xing M,Alzahrani AS,Carson KA,et al.Association between BRAFV600Emutation and recurrence of papillary thyroid cancer[J].J Clin Oncol,2015,33(1):42-50.
[8]Xu Liangzhong,Yang Wentao.The criteria standards of immunohistochemistry results[J].China Oncology,1996,6(4):229-231.[许良中,杨文涛.免疫组织化学反映结果的判断标准[J].中国癌症杂志,1996,6(4):229-231.]
[9]Li Senpeng,Zhang Xiumei,Zhang Rui.BRAF gene mutation and tumor drug resistance[J].Journal of Pharmaceutical Research,2013,32(8):470-472.[李森朋,张岫美,张芮.BRAF基因突变与肿瘤耐药[J].药学研究,2013,32(8):470-472.]
[10]Ilie MI,Lassalle S,Long-Mira E,et al.Diagnostic value of immunohistochemistry for the detection of the BRAFV600Emutation in papillary thyroid carcinoma:Comparative analysis with three DNA-based assays[J].Thyroid,2014,24(5):858-866.
[11]Dong Liru,Yang Hu,Li Shuang,et al.BRAFV600Emutation and expression of its protein in papillary thyroid carcinoma[J].China Oncology,2017,27(4):251-255.[董丽儒,杨虎,李双,等.甲状腺乳头状癌BRAFV600E基因突变及相关蛋白的表达[J].中国癌症杂志,2017,27(4):251-255.]
[12]Miccoli P,Basolo F.BRAF mutation status in papillary thyroid carcinoma:Significance for surgical strategy[J].Langenbecks Arch Surg,2014,399(2):225-228.
[13]Yip L,Nikiforova MN,Carty SE,et al.Optimizing surgical treatment of papillary thyroid carcinoma associated with BRAF mutation[J].Surgery,2009,146(6):1215-1223.
[14]So YK,Son YI,Hong SD,et al.Subclinical lymph node metastasis in papillary thyroid microcarcinoma:A study of 551 resections[J].Surgery,2010,148(3):526-531.
[15]Howell GM,Nikiforova MN,Carty SE,et al.BRAFV600Emutation independently predicts central compartment lymph node metastasis in patients with papillary thyroid cancer[J].Ann Surg Oncol,2013,20(1):47-52.
[16]Lee JW,Koo BS.The prognostic implication and potential role of BRAF mutation in the decision to perform elective neck dissection for thyroid cancer[J].Gland Surgery,2013,2(4):206-211.