涎腺腺样囊性癌组织中HPV感染及p53、p16、EGFR、Cdc2蛋白表达与预后的关系
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摘要
目的初步探讨HPV感染及p53、p16、EGFR及Cdc2表达与涎腺腺样囊性癌(adenoid cystic carcinoma,ACC)预后的关系。方法收集76例涎腺ACC手术标本,分别采用PCR-DNA反向点杂交及免疫组化SP法检测肿瘤组织中HPV-DNA及p53、p16、EGFR及Cdc2表达,收集临床资料并随访。Kaplan-Meier模型分析患者生存情况,Log-rank检验比较生存曲线,多因素Cox回归模型进行预后分析。结果涎腺ACC组织中HPV感染率为0(0/76)。p53、p16、EGFR及Cdc2蛋白在肿瘤组织中的阳性率分别为76.3%(58/76)、57.9%(44/76)、60.5%(46/76)及64.5%(49/76)。p53、p16、EGFR及Cdc2蛋白表达与患者性别、年龄、肿瘤部位、TNM分期及病理类型无关(P均>0.05)。EGFR阳性患者中位总生存期(overall survival,OS)低于阴性患者(χ~2=19.111,P<0.01)。EGFR阳性患者中位无进展生存期(progression-free survival,PFS)低于阴性患者(χ~2=6.621,P<0.01)。Cdc2阳性患者中位OS短于阴性患者(χ~2=3.870,P<0.05)。Cdc2阳性患者中位PFS低于阴性患者(χ~2=6.755,P<0.01)。多因素Cox回归模型分析显示EGFR、Cdc2蛋白表达(RR=13.417、13.075,P均<0.001)是涎腺ACC患者预后的独立危险因素。结论涎腺ACC组织中未检测出HPV感染。p53、p16、EGFR及Cdc2蛋白在涎腺ACC组织中呈不同程度表达,p16不能作为涎腺ACC患者HPV感染状态的替代指标。EGFR及Cdc2阳性表达是涎腺ACC患者预后的独立危险因素,临床对EGFR及Cdc2蛋白表达患者应密切随访。
Purpose To investigate the relationship between HPV infection and p53,p16,EGFR expression and prognosis in patients with salivary adenoid cystic carcinoma(ACC).Methods Totally 76 cases of adenoid cystic carcinoma specimens were selected,PCR-reverse dot blot hybridization was used to detect infection of HPV and SP immunohistochemical method was adopted to detect the expression of p53,p16,EGFR,Cdc2 in tumor tissues. Clinical data were collected and all the patients were followed up. The Kaplan-Meier method was used to estimate median overall survival and the Log-rank test to compare survival curves. Cox regression model was used for multivariate analyses. Results Infection rate of HPV in adenoid cystic carcinoma tissues was 0(0/76). The expression rate of p53,p16,EGFR,Cdc2 protein in adenoid cystic carcinoma tissues were76. 3%(58/76), 57. 9%(44/76), 60. 5%(46/76) and64. 5%(49/76) respectively. There was no correlation of the expression of p53,p16,EGFR and Cdc2 with gender,age,tumor location,TNM stage and histological type of patient. Kaplan-Meier survival analysis showed that EGFR-positive patients had shorter median overall survival rate(OS) than the negative ones(χ~2= 19. 111,P < 0. 001). EGFR-positive patients had shorter median progression-free survival rate(PFS) than the negative ones(χ~2= 6. 621,P < 0. 01). Cdc2 positive patients had shorter median OS than the negative ones(χ~2= 3. 870,P <0. 05). Cdc2 positive patients had shorter median PFS than the negative ones(χ~2= 6. 755,P < 0. 01). Cox regression analysis showed that expression of EGFR and Cdc2 was independent risk factors for the prognosis of patients with salivary gland ACC(relative risk = 13. 417,13. 075,P < 0. 001). Conclusion There is no HPV infection detected in adenoid cystic carcinoma tissues.p53,p16,EGFR and Cdc2 are positively expressed in most salivary adenoid cystic carcinoma. p16 is unsuitable as a surrogate for HPV infection status of patient with ACC. Expression of EGFR and Cdc2 is independent risk factors in the prognosis of patients with salivary gland ACC. For the EGFR or Cdc2 positive patients should be followed up closely.
Purpose To investigate the relationship between HPV infection and p53,p16,EGFR expression and prognosis in patients with salivary adenoid cystic carcinoma(ACC).Methods Totally 76 cases of adenoid cystic carcinoma specimens were selected,PCR-reverse dot blot hybridization was used to detect infection of HPV and SP immunohistochemical method was adopted to detect the expression of p53,p16,EGFR,Cdc2 in tumor tissues. Clinical data were collected and all the patients were followed up. The Kaplan-Meier method was used to estimate median overall survival and the Log-rank test to compare survival curves. Cox regression model was used for multivariate analyses. Results Infection rate of HPV in adenoid cystic carcinoma tissues was 0(0/76). The expression rate of p53,p16,EGFR,Cdc2 protein in adenoid cystic carcinoma tissues were76. 3%(58/76), 57. 9%(44/76), 60. 5%(46/76) and64. 5%(49/76) respectively. There was no correlation of the expression of p53,p16,EGFR and Cdc2 with gender,age,tumor location,TNM stage and histological type of patient. Kaplan-Meier survival analysis showed that EGFR-positive patients had shorter median overall survival rate(OS) than the negative ones(χ~2= 19. 111,P < 0. 001). EGFR-positive patients had shorter median progression-free survival rate(PFS) than the negative ones(χ~2= 6. 621,P < 0. 01). Cdc2 positive patients had shorter median OS than the negative ones(χ~2= 3. 870,P <0. 05). Cdc2 positive patients had shorter median PFS than the negative ones(χ~2= 6. 755,P < 0. 01). Cox regression analysis showed that expression of EGFR and Cdc2 was independent risk factors for the prognosis of patients with salivary gland ACC(relative risk = 13. 417,13. 075,P < 0. 001). Conclusion There is no HPV infection detected in adenoid cystic carcinoma tissues.p53,p16,EGFR and Cdc2 are positively expressed in most salivary adenoid cystic carcinoma. p16 is unsuitable as a surrogate for HPV infection status of patient with ACC. Expression of EGFR and Cdc2 is independent risk factors in the prognosis of patients with salivary gland ACC. For the EGFR or Cdc2 positive patients should be followed up closely.
引文
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[11]Huo Z,Meng Y X,Wu H W,et al.Adenoid cystic carcinoma of the tracheobronchial tree:clinicopathologic and immunohistochemical studies of 21 cases[J].Int J Clin Exp Pathol,2014,7(11):7527-7535.
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[13]Yang J Q,Liu H X,Liang Z,et al.Over-expression of p53,p21and Cdc2 in histologically negative surgical margins is correlated with local recurrence of laryngeal squamous cell carcinoma[J].Int J Clin Exp Pathol,2014,7(7):4295-4302.
[14]刘宏侠,孙玉满,杨俊泉,等.喉癌与手术切缘组织PCNA和Cdc2表达与局部复发相关性研究[J].中华肿瘤防治杂志,2015,21(21):1701-1705.
[15]Wada S,Yue L,Furuta I.Prognostic significance of p34cdc2 expression in tongue squamous cell carcinoma[J].Oral Oncol,2004,40(2):164-169.
[16]孙玉满,刘宏侠,杨俊泉,等.细胞周期依赖性蛋白激酶1(Cdk1/p34cdc2)对喉癌术后局部复发的预测价值[J].临床与实验病理学杂志,2015,31(3):293-297.
[2]Hühns M,Simm G,Erbersdobler A,Zimpfer A.HPV infection,but Not EBV or HHV-8 infection,is associated with salivary gland tumours[J].Bio Med Res Int,2015,2015:829349.
[3]Ferlay J,Soerjomataram I,Ervik M,et al.Estimated cancer incidence,mortality and prevalence worldwide in 2012[M].Lyon:IARC Press,2012.
[4]Boland J M,Mc Phail E D,García J J,et al.Detection of human papilloma virus and p16 expression in high-grade adenoid cystic carcinoma of the head and neck[J].Mod Pathol,2012,25(4):529-536.
[5]Justin A B,Takenori O,Edward B S,et al.Human papillomavirus-related carcinoma with adenoid cystic-like features:a peculiar variant of head and neck cancer restricted to the sinonasal tract[J].Am J Surg Pathol,2013,37(6):836-844.
[6]霍真,孟云霄,凌庆,等.肺腺样囊性癌中Myb与预后及p16与HPV感染的关系[J].诊断病理学杂志,2016,23(2):81-84.
[7]Isayeva T,Said-Al-Naief N,Ren Z,et al.Salivary mucoepidermoid carcinoma:demonstration of transcriptionally active human papillomavirus 16/18[J].Head Neck Pathol,2013,7(2):135-148.
[8]Lassen P,Eriksen J G,Hamilton-Dutoit S,et al.Effect of HPVassociated p16INK4A expression on response to radiotherapy and survival in squamous cell carcinoma of the head and neck[J].J Clin Oncol,2009,27(12):1992-1998.
[9]Xing D,Schoolmeester J K,Ren Z,et al.Lower female genital tract tumors with adenoid cystic differentiation:p16 expression and high-risk HPV detection[J].Am J Surg Pathol,2016,40(4):529-536.
[10]Jiang L C,Huang S Y,Zhang D S,et al.Expression of beclin 1in primary salivary adenoid cystic carcinoma and its relation to Bcl-2 and p53 and prognosis[J].Braz J Med Biol Res,2014,47(3):252-258.
[11]Huo Z,Meng Y X,Wu H W,et al.Adenoid cystic carcinoma of the tracheobronchial tree:clinicopathologic and immunohistochemical studies of 21 cases[J].Int J Clin Exp Pathol,2014,7(11):7527-7535.
[12]Wang W M,Zhao Z L,Zhang W F,et al.Role of hypoxia-inducible factor-1αand CD146 in epidermal growth factor receptor-mediated angiogenesis in salivary gland adenoid cystic carcinoma[J].Mole Med Rep,2015,12(3):3432-3438.
[13]Yang J Q,Liu H X,Liang Z,et al.Over-expression of p53,p21and Cdc2 in histologically negative surgical margins is correlated with local recurrence of laryngeal squamous cell carcinoma[J].Int J Clin Exp Pathol,2014,7(7):4295-4302.
[14]刘宏侠,孙玉满,杨俊泉,等.喉癌与手术切缘组织PCNA和Cdc2表达与局部复发相关性研究[J].中华肿瘤防治杂志,2015,21(21):1701-1705.
[15]Wada S,Yue L,Furuta I.Prognostic significance of p34cdc2 expression in tongue squamous cell carcinoma[J].Oral Oncol,2004,40(2):164-169.
[16]孙玉满,刘宏侠,杨俊泉,等.细胞周期依赖性蛋白激酶1(Cdk1/p34cdc2)对喉癌术后局部复发的预测价值[J].临床与实验病理学杂志,2015,31(3):293-297.