Evaluation of chemoresistance markers in women with epithelial ovarian carcinoma

Objective. Preliminary studies have suggested that lung resistance protein (LRP), multidrug resistance protein (MRP), and p27 may be useful markers of chemoresistance. Our goal was to evaluate the expression of LRP, MRP, and p27 in normal ovaries and chemosensitive and chemoresistant ovarian carcino mas. Methods. Fourteen women with normal ovaries and fifty women with epithelial ovarian carcinoma who underwent cytoreductive surgery from 1996 through 19 98 had specimens stained with immunocytochemistry for LRP, MRP, and p27. Al l women received paclitaxel/platinum-based chemotherapy. Twenty-nine women had a disease-free survival (DFS) of at least 12 months after completion of chemotherapy (sensitive) and 21 women had persistent disease during treatm ent (resistant). Results. Evaluation of LRP expression revealed significant differences betw een the normal ovaries and cancers in both the epithelial (57% vs 90%, P = 0.03) and stromal (86% vs 32%, P = 0.001) components. Evaluation of MRP exp ression revealed significant differences between normal ovaries and cancers in the epithelial component (7% vs 66%, P = 0.001) but not in the stromal component (14% vs 4%, P = 0.1). Evaluation of p27 revealed significant redu ctions in expression in cancers compared with normal ovaries for both the e pithelial (90% vs 55%, P = 0.02) and stromal (88% vs 5%, P = 0.001) compone nts. Comparison between the chemosensitive and chemoresistant groups reveal ed no significant differences in expression of LRP and MRP, in either the e pithelial or stromal component, but significantly lower levels of p27 were expressed in the epithelial component of the chemoresistant group (P = 0.01 ). Conclusions. The expression of LRP, MRP, and p27 is significantly different in ovarian cancers compared with normal ovaries. Low levels of p27 express ion are associated with chemoresistance; however, LRP and MRP expression ar e not prognostic for chemosensitivity. (C) 2001 Academic Press.