细胞周期蛋白D1、CDK4在乳腺癌中的表达及其临床意义

目的：研究乳腺癌组织周期蛋白D1、CDK4的蛋白表达定位、表达水平，及与P21蛋白表达、与临床病理指标的关系及其预后意义。方法：①应用免疫组织化学染色方法，检测106例乳腺癌组织石蜡切片上的周期蛋白D1、CDK4的蛋白定位和蛋白表达，比较其与P21的蛋白表达，与临床病理学指标，如病理类型、组织学分型、组织学分级、淋巴结状态、雌激素受体状态、TNM分期等之间的关系；②对周期蛋白D1、CDK4、P21及临床病理指标如肿瘤的组织学分级、淋巴结状态、TNM分期、ER状态等，应用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：①周期蛋白D1表达定位于细胞核、CDK4的表达位于细胞质和细胞核，周期蛋白D1的阳性率为30.2%，CDK4的阳性率为53.8%。②周期蛋白D1及CDK4的表达与乳腺癌的病理诊断组织学分型、组织学分级、ER状态、临床TNM分期、淋巴结状态、P21蛋白表达水平无关（P＞0.05)。周期蛋白D1的蛋白表达与DCK4的蛋白表达相关（P＜0.05)。③单因素分析提示影响140个月无瘤生存率及总生存率的因素有：临床TNM分期、组织学分级、腋淋巴结状态、周期蛋白D1的蛋白表达（P＜0.05)。在无腋淋巴结转移亚组周期蛋白D1蛋白表达单因素生存分析无统计学意义（P＞0.05)，在腋淋巴结有转移亚组周期蛋白D1是影响140个月无瘤生存率和总生存率的因素（P＜0.01)。④多因素生存分析结果表明周期蛋白D1、P21蛋白表达、组织学分级是影响乳腺癌患者无瘤生存率和总生存率的独立预后因素（P＜0.05)。结论：周期蛋白D1、P21的蛋白表达水平及组织学分级可能是判断乳腺癌术后生存的有效指标，综合应用这些指标可能更有帮助。

Protein expression of Cyclin D1,CDK4 in breast cancer as related to prognosis

Purpose：To study the localization and expression level of cyclin D1 and CDK4 protein in breast cancer, and their relationship to P21 protein and clinicopathoogical factors as well as the prognostic factors in 106 breast cancer patients. Methods：Using immunohistochemistry method the cyclin D1 and CDK4 protein were detected in the formalin-fixed paraffin-embedded breast cancer sections,the relationship between cyclin D1, CDK4 to P21 protein expression and clinicopathological factors such as TNM stage, axillary lymph node metastases, ER status etc. were analyzed. The Kaplan-Meier method (Log-rank test) was used for univariate survival analysis and the Cox proportional hazard model for multivariate survival analysis, we studied the prognostic role of the protein expression of cyclin D1, CDK4, P21 and clinicopathological factors such as axillary lymph node metastases, TMN stage,age and ER status etc. in 106 breast cancer patients. Results：①Cyclin D1 showed nuclear staining and CDK4 both in cytoplasm and nuclear in breast cancer cells. 30.2% of the tumor showed cyclin D1 positive, and 53.8% showed CDK4 positive. ②The expression level of both cyclin D1 and CDK4 protein did not correlate with histological classification, histological grade, ER status, clinical TNM stage, axillary lymph node metastases and P21 protein expression (P＞0.05). The expression level of cyclin D1 protein correlated with CDK4 protein expression level (P＜0.05). ③Univariate survival analyses indicated that clinical TNM stage, histological grade, axillary lymph node status, cyclin D1 and cyclin E were associated with both overall survival and disease free survival (P＜0.05). In axillary lymph node positive subgroup, cyclin D1 was associated with overall survival and disease free survival (P＜0.05), but in axillary lymph node negative subgroup cyclin D1 was not associated with overall survival and disease free survival (P＞0.05). ④Multivariate analyses indicated that histological grade, cyclin D1 and P21 were independent prognositic factors for both overall survival and disease free survival (P＜0.05). Conclusions：The expression level of cyclin D1, P21 protein and histological grade were potential prognostic factors in post-operative breast cancer patients, it will be more helpful if combination of these factors is considered.