Monoclonal antibody C219 detection of the multidrug-resistant protein P-glycoprotein in routinely processed tissues: a study of 36 cases of ovarian carcinoma.

Abstract

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.