Expression of folate binding protein as a prognostic factor for response to platinum-containing chemotherapy and survival in human ovarian cancer

Abstract

Overexpression of the folate binding protein (FBP) is a common feature in epithelial ovarian cancer, but its prognostic significance is not clearly understood. We investigated whether FBP in epithelial ovarian cancer specimens is a predictor of response to chemotherapy and survival. Between 1990 and 1995, 99 patients with epithelial ovarian cancer underwent primary surgery and were treated with chemotherapeutic regimens including platinum derivatives. First-line chemotherapy was performed in 58 patients with residual disease and in 41 patients without residual disease after primary laparotomy. FBP expression level was determined in frozen specimens by cyto-fluorimetric assay using the MOv 18 monoclonal antibody (MAb). Association of FBP fluorescence index (FI) with clinical characteristics, response to chemotherapy, and survival was studied by univariate and multivariate analysis. In the 58 patients with residual disease after primary surgery, failure to respond to chemotherapy (complete or partial remission) was about 15-fold higher (95% confidence interval, 2.96-77.43) when tumors had FBP FI above the median value (FBP FI = 3.25). FBP FI was not a predictor of survival in the entire series of tumors (99 patients). However, in the subgroup of 58 patients with residual disease after primary surgery, survival analysis confirmed the disadvantage observed with respect to response to chemotherapy in patients expressing FBP FI above the median value (hazard ratio 2.01; 95% confidence interval 0.95-4.24). In conclusion, higher levels of FBP expression might be a predictor of chemotherapy response failure in ovarian cancer. In patients with residual disease after primary surgery, FBP FI could represent a valuable prognostic marker for survival.