TopoⅡα蛋白在不同分子亚型乳腺癌中的表达及其预后价值

Expression of Topomerase Ⅱα Protein in Different Molecular Subtypes of Breast Cancer and Their Prognostic Values

目的:探讨拓扑异构酶Ⅱ(TopoisomeraseⅡ,TopoⅡα)蛋白在三阴性乳腺癌和HER2高表达型乳腺癌中的表达及其与预后的关系。方法:选取2004年1月至7月天津医科大学附属肿瘤医院乳腺癌患者202例为研究对象,其中三阴性乳腺癌101例,HER2高表达型乳腺癌101例,采用免疫组化方法检测TopoⅡα蛋白在两型乳腺癌中的表达及其与预后的关系。结果:TopoⅡα蛋白在三阴性乳腺癌中的表达率为51.9%,在HER2过表达型乳腺癌中的表达率为48.9%,二者差异无统计学意义(P>0.05)。TopoⅡα蛋白表达水平与两型乳腺癌患者月经状况、肿瘤大小、临床分期、腋下淋巴结转移状况、组织学分级、病理学类型等临床病理指标均无相关性(P>0.05)。HER2高表达型乳腺癌中,TopoⅡα蛋白阳性和阴性组5年无瘤生存率为81.0%和60.5%,5年总生存率分别为92.1%和76.3%,两组差异均具有统计学意义(P=O.037,P=0.047)。多因素分析结果显示TopoⅡα蛋白表达可以作为HER2过表达型乳腺癌的独立预后因子。三阴性乳腺癌中,TopoⅡα蛋白阳性和阴性组5年无瘤生存率分别为69.7%和82.4%,差异具有统计学意义(P=0.044),5年总生存率分别为75.0%和84.5%,二者差异无统计学意义(P=0.927)。结论:HER2过表达型乳腺癌,TopoⅡα蛋白阳性的患者预后较好,提示此型乳腺癌患者可从蒽环类化疗药物中获益,为临床用药提供一定的理论依据在三阴性乳腺癌患者中,TopoⅡα蛋白阳性表达患者较TopoⅡα蛋白阴性预后差,对于临床判断预后具有指导意义。

Objective： To compare triple negative and human epidermal growth factor receptor （ HER2 ） overexpression breast cancer in terms of Topoisomerase （ Topo ） Ⅱα expression in relation to reasonable clinical prognosis and rational use of drugs to provide better theoretical basis. Methods： A total of 202 breast cancer patients were selected from Tianjin Medical University Cancer Hospital after surgery between January and July, 2004. Based on the expression of estrogen receptor, progesterone receptor, and HER2, 101 triple negative breast cancer cases and 101 HER2-overexpressing breast cancer cases were setected. Using immunohistochemical methods, Topo Ⅱα protein expression in the two types of breast cancer and its relation to prognosis were determined. Results： Topo Ⅱα protein expression was 51.9% in HER2 overexpression breast cancer and 48.9% in triple negative breast cancer; the difference was not sig- nificant （ P 〉 0.05 ）. Topo Ⅱα protein expression had no correlation with age, tumor size, clinical stage, axillary lymph node status, his- tological grade, pathological type, or other clinicopathological parameters （ P 〉 0.05 ）. The 5-year disease-free survival （DFS） rate was 81.0% in the Topo Ⅱα and HER2 co-expression subtype, and 60.5% in the Topo Ⅱα-negative HER2-positive group; the difference was statistically significant （ P = 0.037 ）. The 5-year overall survival rate was 92.1% in the Topo Ⅱα and HER2 protein co-expression sub- type, and 76.3% in the Topo Ⅱα-negative HER2-positive group; the difference was statistically significant （ P = 0.047 ）. Multivariate Cox regression analysis showed that Topo IIct was a prognostic factor of HER2-overexpressing breast cancer. For triple negative breast cancer, the Topo Ⅱα-positive and -negative 5-year DFS rates were 69.7% and 82.4%（ significantly different, P = 0.044 ）, and the OS rates were 75.0% and 84.5% （ not significantly different, P = 0.927 ）. Conclusion： For HER2 overexpressing breast cancer, patients with Topo Ⅱα-positive expression have better prognosis than those who are Topo Ⅱα-negative. Thus, these patients can benefit from an- thracycline chemotherapy, providing a theoretical basis for its clinical use. For triple negative breast cancer, patients with Topo Ⅱα-posi-tive expression had poorer prognosis. Hence, close attention should be paid to the clinical prognosis of these patients.