Rutledge M L, Robey-Cafferty S S, Silva E G, Bruner J M
Department of Pathology, University of Texas M. D. Anderson Cancer Center, Houston.
Mod Pathol. 1990 May;3(3):298-301.
P-glycoprotein is a membrane protein found in high levels in multidrug-resistant (MDR) tumor cells and is associated with in vitro and clinical resistance of neoplasms to a wide variety of structurally unrelated oncolytic agents. We retrospectively investigated the presence of P-glycoprotein in 36 patients with treated, high grade ovarian carcinomas by using a murine monoclonal antibody (C219). The patients were selected on the basis of their complete response (11 patients) or nonresponse (25 patients) to chemotherapy. Routinely processed tissue sections from pre- and postchemotherapy surgical tissue samples were processed by a standard immunohistochemical method. Sections of tumor from both pre- and postchemotherapy specimens from the responder group were all negative, as were the prechemotherapy specimens from the nonresponder group. Four of the 25 (15%) nonresponders' postchemotherapy tissues were positive, predominantly in areas of histologically undifferentiated tumor. The cellular localization of P-glycoprotein in normal, untreated tissues was also investigated using C219, and its presence in various luminal epithelia of the gastrointestinal tract, kidney, and liver are consistent with its proposed normal function as a toxin/drug-export protein. Our overall results indicate that P-glycoprotein can be detected in routinely processed tissues by standard methods. The presence of P-glycoprotein in some patients with treated ovarian carcinomas is associated with nonresponse to standard chemotherapy treatment.
P-糖蛋白是一种在多药耐药(MDR)肿瘤细胞中高表达的膜蛋白,与肿瘤在体外及临床上对多种结构不相关的溶瘤药物产生耐药有关。我们采用鼠单克隆抗体(C219)对36例接受过治疗的高级别卵巢癌患者进行回顾性研究,检测P-糖蛋白的表达情况。根据患者对化疗的完全缓解(11例)或无反应(25例)进行分组。化疗前后手术组织样本的常规处理切片采用标准免疫组织化学方法进行检测。缓解组化疗前后肿瘤标本切片均为阴性,无反应组化疗前标本也为阴性。25例无反应患者中,4例(15%)化疗后组织呈阳性,主要位于组织学上未分化的肿瘤区域。我们还使用C219研究了P-糖蛋白在正常未治疗组织中的细胞定位,其在胃肠道、肾脏和肝脏的各种腔上皮中的存在与其作为毒素/药物输出蛋白的正常功能一致。我们的总体结果表明,通过标准方法可以在常规处理的组织中检测到P-糖蛋白。在一些接受治疗的卵巢癌患者中,P-糖蛋白的存在与对标准化疗治疗无反应有关。