乳腺癌细胞中p16、p21、cyclinD1的表达及临床意义

目的:探讨p16、p21和cyclinD1蛋白在乳腺癌组织中的表达及其临床意义。方法:应用免疫组织化学染色方法,检测60例乳腺癌组织石蜡切片上p16、p21和cyclinD1蛋白的表达,比较其与临床病理学指标之间的关系;用Kaplan-Meier法Log-rank检验进行单因素生存分析,应用Cox比例风险模型进行多因素生存分析。结果:p16、p21、CyclinD1蛋白阳性表达率分别为53.3%、58.3%、41.7%,阳性产物主要位于细胞核中。p16蛋白的表达与组织学分级(P<0.05)及淋巴结转移(P<0.01)相关。p21蛋白的表达与淋巴结转移相关(P<0.05)。cyclinD1蛋白的表达与ER相关(P<0.01)。p16蛋白的表达与p21、cyclinD1蛋白表达不相关(P>0.05)。p21蛋白表达与cyclinD1蛋白表达相关(P<0.05)。单因素生存分析提示,影响总生存率的因素有:组织学分级、淋巴结转移、ER和p16、p21、cyclinD1蛋白(P<0.05)。多因素生存分析结果表明,组织学分级、淋巴结转移、ER状态和p16、cyclinD1蛋白是影响乳腺癌患者总生存率的独立预后因素(P<0.05)。结论:p16、p21蛋白的失表达和cyclinD1蛋白的过表达可能参与了乳腺癌的发生和发展。p16、p21蛋白是判断乳腺癌浸润转移的客观指标,cyclinD1蛋白表达与ER有关。组织学分级、淋巴结转移、ER以及p16、p21、cyclinD1蛋白表达可能是判断乳腺癌患者术后生存的有效指标,综合考虑这些指标对判断乳腺癌的预后、合理确定治疗方案具有重要意义。

Expressions of p16, p21, and cyclinD1 in breast cancer cells and their clinical significance

Objective: To study the expression of p16 ,p21 and cyclinD1 proteins and their clinical significance.Methods : The p16 ,p21 and cyclinD1 proteins were detected with immunohistochemical stain method in 60 breast cancer tissues. The relationship between p16, p21, cyclinD1 and some clinicopathological factors were analyzed with c2 test. The Kaplan-Meier (Log-rank test) was used for univariate survival analysis and Cox proportional hazard model for multivariate survival analysis.Results: The positive p16, p21 and cyclinD1 were mostly located in nucleus with rates of 53.3%,58.3%,and 41.7% respectively. The expression level of p16 protein correlated with histological grade (P<0.05)and axillary lymph node metastases(P<0.01).The expression level of p21 protein correlated with axillary lymph node metastases(P<0.05). The expression level of CyclinD1 protein had a significant correlation with ER status(P<0.01). There was a correlation between p21 and cyclinD1(P<0.05),while no correlation between p16 and cyclinD1 or p21 was found(P>0.05). Univariate survival analyses indicated that histological grade, axillary lymph node metastases, ER status, p16 ,p21 and cyclinD1 were associated with overall survival(P<0.05). Multivariate analyses showed that histological grade, axillary lymph node metastases, ER status, p16 and cyclinD1 were independent prognostic factors for overall survival(P<0.05).Conclusions: The underexpression of p16 and p21, and the overexpression of cyclinD1 may play a significant role in the incidence and development of breast cancer. The underexpressions of p16 and p21 might be important indicators for axillary lymph node metastases, and the expression of cyclinD1 is correlated with ER status. Histological grade, axillary lymph node metastases, ER status and the expressions of p16, p21 and cyclinD1 protein are potential prognostic indicators in breast cancer, so combination of these factors will be more helpful for treating breast cancer