乳腺癌相关蛋白表达分析及与临床预后关系的研究
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摘要
目的:回顾性分析405例乳腺癌患者临床病理参数与预后的关系。研究乳腺癌组织中相关蛋白的表达与患者预后的相关性,对乳腺癌的分子分型进行初步探讨。
方法:收集2000年在中国医学科学院肿瘤医院进行手术的乳腺癌病例的临床及病理资料。将这些病例的蜡块标本制成组织芯片,应用免疫组化技术研究PTEN,Ki-67,Bcl-2,BRCA-1,CK5/6蛋白表达情况。分析各蛋白表达与临床病理参数及预后的关系。
结果:全组405例患者均接受手术治疗,术后以骨转移和肺转移为丰。患者中共70例死亡,生存时间4～94个月,平均64.59个月,中位生存期71个月。单因素生存分析结果显示,临床分期、ER、PR、Her-2、p53、PTEN、Ki-67、Bcl-2和CK5/6蛋白的表达及分子分型与病人的总生存期(OS)显著相关,可作为评价乳腺癌预后的候选指标。而临床分期、ER、PR、Her-2、p53、Ki-67、Bcl-2、CK5/6蛋白的表达与病人的无病生存(DFS)显著相关,可作为预测乳腺癌复发转移的候选指标。Cox多因素生存分析显示PTEN、Ki-67、Bcl-2、CK5/6及TNM分期是与总生存相关的独立预后因素。而TNM分期、Ki-67、PR是与无病生存相关的独立预后因素。
结论:乳腺癌的不同分子分型对于乳腺癌的预后具有一定的价值,可作为评价乳腺癌预后的因素之一。PTEN、Ki-67、Bcl-2、CK5/6、TNM分期可作为评价总生存的指标。而分期、Ki-67、PR可作为评价无病生存的指标。
Objective:To study the relationships between clinical and pathological parameters and prognosis retrospectively in 405 patients with breast cancer.Analyze the correlations between related proteins' expression and patients' prognosis.Study the molecular classification in breast cancer patients.
Methods:Clinical and pathological parameters of breast cancer patients who had been operated in the Cancer Hospital,Chinese Academy of Medical Sciences in the 2000 were collected.Tissue microarrays were established with wax blocked tissue.The expressions of PTEN,Ki-67,Bcl-2,BRCA-1 and CK5/6 proteins were measured with immunohistochemistry technique.The relationships between the expression of clinical and pathological parameters and prognosis were analyzed.
Results:All of 405 patients received operation and 70 of them died.Among patients with metastasis disease,most of them were bone and lung metastasis.The survival period were 4～94 months with the median of 71 months.Univariate analysis suggests that clinical staging,expressions of ER,PR,Her-2,p53,PTEN,Ki-67,Bcl-2 proteins,and molecular typing were significantly correlated with patients' over-all survivals(OS),and could be regarded as predictors to evaluate the prognosis of breast cancer patients.Clinical staging, expressions of ER,PR,Her-2,p53,Ki-67,Bcl-2 and CK5/6 proteins were significantly correlated with patients' disease-free survivals(DFS) and could be regarded as predictors of recurrence and metastasis in breast cancer patients.Cox multiple factors survival analysis suggests that PTEN,Ki-67,Bcl-2,CK5/6 proteins expression and staging are independent prognosis factors which are correlated with OS.Staging,Ki-67 and PR status were independent prognosis factors which are correlated with DFS.
Conclusion:Molecular classification contributes to the prognosis of breast cancer patients,and could be regarded as one of the factors for evaluating survival time.PTEN, Ki-67,Bcl-2 and CK5/6 proteins expression and staging are independent prognosis factors which are correlated with OS.Staging,Ki-67 and PR status were independent prognosis factors which are correlated with DFS.
方法:收集2000年在中国医学科学院肿瘤医院进行手术的乳腺癌病例的临床及病理资料。将这些病例的蜡块标本制成组织芯片,应用免疫组化技术研究PTEN,Ki-67,Bcl-2,BRCA-1,CK5/6蛋白表达情况。分析各蛋白表达与临床病理参数及预后的关系。
结果:全组405例患者均接受手术治疗,术后以骨转移和肺转移为丰。患者中共70例死亡,生存时间4～94个月,平均64.59个月,中位生存期71个月。单因素生存分析结果显示,临床分期、ER、PR、Her-2、p53、PTEN、Ki-67、Bcl-2和CK5/6蛋白的表达及分子分型与病人的总生存期(OS)显著相关,可作为评价乳腺癌预后的候选指标。而临床分期、ER、PR、Her-2、p53、Ki-67、Bcl-2、CK5/6蛋白的表达与病人的无病生存(DFS)显著相关,可作为预测乳腺癌复发转移的候选指标。Cox多因素生存分析显示PTEN、Ki-67、Bcl-2、CK5/6及TNM分期是与总生存相关的独立预后因素。而TNM分期、Ki-67、PR是与无病生存相关的独立预后因素。
结论:乳腺癌的不同分子分型对于乳腺癌的预后具有一定的价值,可作为评价乳腺癌预后的因素之一。PTEN、Ki-67、Bcl-2、CK5/6、TNM分期可作为评价总生存的指标。而分期、Ki-67、PR可作为评价无病生存的指标。
Objective:To study the relationships between clinical and pathological parameters and prognosis retrospectively in 405 patients with breast cancer.Analyze the correlations between related proteins' expression and patients' prognosis.Study the molecular classification in breast cancer patients.
Methods:Clinical and pathological parameters of breast cancer patients who had been operated in the Cancer Hospital,Chinese Academy of Medical Sciences in the 2000 were collected.Tissue microarrays were established with wax blocked tissue.The expressions of PTEN,Ki-67,Bcl-2,BRCA-1 and CK5/6 proteins were measured with immunohistochemistry technique.The relationships between the expression of clinical and pathological parameters and prognosis were analyzed.
Results:All of 405 patients received operation and 70 of them died.Among patients with metastasis disease,most of them were bone and lung metastasis.The survival period were 4～94 months with the median of 71 months.Univariate analysis suggests that clinical staging,expressions of ER,PR,Her-2,p53,PTEN,Ki-67,Bcl-2 proteins,and molecular typing were significantly correlated with patients' over-all survivals(OS),and could be regarded as predictors to evaluate the prognosis of breast cancer patients.Clinical staging, expressions of ER,PR,Her-2,p53,Ki-67,Bcl-2 and CK5/6 proteins were significantly correlated with patients' disease-free survivals(DFS) and could be regarded as predictors of recurrence and metastasis in breast cancer patients.Cox multiple factors survival analysis suggests that PTEN,Ki-67,Bcl-2,CK5/6 proteins expression and staging are independent prognosis factors which are correlated with OS.Staging,Ki-67 and PR status were independent prognosis factors which are correlated with DFS.
Conclusion:Molecular classification contributes to the prognosis of breast cancer patients,and could be regarded as one of the factors for evaluating survival time.PTEN, Ki-67,Bcl-2 and CK5/6 proteins expression and staging are independent prognosis factors which are correlated with OS.Staging,Ki-67 and PR status were independent prognosis factors which are correlated with DFS.
引文
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