子宫内膜浆液性乳头状癌组织中Her－2／neu基因的扩增和蛋白表达及其意义  

Clinical significance of Her-2/neu status in patients with uterine papillary serous carcinoma

作　　者：任玉兰[1] 王华英[1] 周晓燕[2] 单波儿[1] 杨文涛[2] 沈磊[2] 施达仁[2] 

机构地区：[1]复旦大学附属肿瘤医院妇瘤科,上海200032 [2]复旦大学附属肿瘤医院病理科,上海200032

出　　处：《中华妇产科杂志》2010年第5期367-371,共5页Chinese Journal of Obstetrics and Gynecology

基　　金：上海市科学技术委员会科研计划（08411961900）

摘　　要：目的 检测Her-2/neu基因在子宫内膜浆液性乳头状癌（UPSC）中的扩增和蛋白表达情况,并分析其临床意义.方法 回顾性分析1996年1月-2006年1月在复旦大学附属肿瘤医院手术治疗的36例UPSC患者的临床病理资料,分别用显色原位杂交和免疫组化法检测Her-2/neu基因在UPS组织中的扩增和蛋白表达情况,并对两种方法进行对比分析;采用单因素log-rank检验、多因素Cox同归法分析影响UPSC预后的因素.同时随机选择同期收治、临床资料完整的136例Ⅰ型子宫内膜样腺癌作为对照,行免疫组化法检测其Her-2/neu蛋白的表达.结果 免疫组化法检测显示,UPSC患者Her-2/neu蛋白阳性表达率为36.1%（13/36）, Ⅰ型子宫内膜样腺癌患者为6.6%（9/136）,两者比较,差异有统计学意义（P=0.000）.显色原位杂交法检测显示,UPSC患者Her-2/neu基因高度扩增率为11.1%（4/36）.显色原位杂交和免疫组化法检测的符合率为100%.36例UPSC患者中,手术病理分期Ⅲ～Ⅳ患者的Her-2/neu蛋白阳性表达率为50.0%（11/22）,明显高于Ⅰ～Ⅱ期患者的14.3%（2/14,P=0.030）;而不同肌层浸润深度、病理类型构成、病理分化程度及有无脉管侵犯、p53蛋白、雌激素受体（ER）、孕激素受体（PR）表达患者间Her-2/neu蛋白阳性表达率比较,差异均无统计学意义（P〉0.05）.单因素分析显示,Her-2/neu蛋白表达、肌层浸润深度和手术病理分期是影响UPSC患者预后的危险因素（P〈0.05）;多因素分析显示,Her-2/neu蛋白表达和肌层浸润深度是影响UPSC患者预后的独立危险因素（P〈0.05）.Her-2/neu蛋白阳性表达的13例患者中,8例子化疗者平均牛存时间（20个月）较5例未化疗者（42个月）短,但差异无统计学意义（P=O.370）.结论 UPSC组织中Her-2/neu蛋白阳性表达与手术分期晚显著相关,Her-2/neu蛋白表达和肌层浸润深度是影响UPSC预后的独立危险因素.Objective The purpose of this study was to evaluate gene amplification by chromogenic in situ hybridization （CISH） and the protein expression of Her-2/neu gene in patients with uterine papillary serous carcinoma （UPSC） and to determine its prognostic value. Methods Thirty-six patients with confirmed pathologic diagnosis of UPSC in Cancer Hospital of Fudan University from Jan. 1996 to Jan. 2006, were analysed retrospectively. CISH was performed to assess Her-2/neu gene amplification, and protein expression was evaluated by immunohistochemistry （ IHC ）. The prognostic factors were analyzed by log-rank test or Cox proportional hazard model. Results Among 36 cases with UPSC, 13 patients （36. 1% ） showed moderate staining （＋＋） to strong staining （＋＋＋） for Her-2/neu protein, while amplification of the Her-2/neu gene by CISH was observed in 4 of the 36 （ 11.1% ） cases. Her-2/neu protein over-expression was significantly associated with advanced surgical stage and worse prognosis by univariate analysis （P = 0. 030 and P = 0. 002, respectively）, while the multivariate analysis shown that only Her-2/neu protein over-expression and deep myometrial invasion were associated with a poor prognosis （ P 〈 0. 05 ）. In 13 patients with Her-2/neu protein over-expression, the mean survival period with chemotherapy was shorter than those without chemotherapy （ 20 vs. 42 months, P = 0. 370）. Conclusion Her-2/neu protein over- expression is significantly associated with advanced surgical stage UPSC and poor survival outcome, and might reduce the chemotherapy sensitivity.

关 键 词：子宫内膜肿瘤 癌 乳头状 基因 ERBB-2 受体 erbB-2 预后 

分 类 号：R737.33[医药卫生—肿瘤]