CAJ | 학술논문

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.
목적 검측Her-2/neu기인재자궁내막장액성유두상암(UPSC)중적확증화단백표체정황,병분석기림상의의.방법 회고성분석1996년1월-2006년1월재복단대학부속종류의원수술치료적36례UPSC환자적림상병리자료,분별용현색원위잡교화면역조화법검측Her-2/neu기인재UPS조직중적확증화단백표체정황,병대량충방법진행대비분석;채용단인소log-rank검험、다인소Cox동귀법분석영향UPSC예후적인소.동시수궤선택동기수치、림상자료완정적136례Ⅰ형자궁내막양선암작위대조,행면역조화법검측기Her-2/neu단백적표체.결과 면역조화법검측현시,UPSC환자Her-2/neu단백양성표체솔위36.1%(13/36), Ⅰ형자궁내막양선암환자위6.6%(9/136),량자비교,차이유통계학의의(P=0.000).현색원위잡교법검측현시,UPSC환자Her-2/neu기인고도확증솔위11.1%(4/36).현색원위잡교화면역조화법검측적부합솔위100%.36례UPSC환자중,수술병리분기Ⅲ～Ⅳ환자적Her-2/neu단백양성표체솔위50.0%(11/22),명현고우Ⅰ～Ⅱ기환자적14.3%(2/14,P=0.030);이불동기층침윤심도、병리류형구성、병리분화정도급유무맥관침범、p53단백、자격소수체(ER)、잉격소수체(PR)표체환자간Her-2/neu단백양성표체솔비교,차이균무통계학의의(P>0.05).단인소분석현시,Her-2/neu단백표체、기층침윤심도화수술병리분기시영향UPSC환자예후적위험인소(P<0.05);다인소분석현시,Her-2/neu단백표체화기층침윤심도시영향UPSC환자예후적독립위험인소(P<0.05).Her-2/neu단백양성표체적13례환자중,8례자화료자평균우존시간(20개월)교5례미화료자(42개월)단,단차이무통계학의의(P=O.370).결론 UPSC조직중Her-2/neu단백양성표체여수술분기만현저상관,Her-2/neu단백표체화기층침윤심도시영향UPSC예후적독립위험인소.
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 13patients 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.