Rationale for folate receptor alpha targeted therapy in “high risk” endometrial carcinomas

Advanced and recurrent endometrial cancers account for the majority of deaths from this disease with limited therapeutic options. High grade, and nonendometrioid histology, pathologically characterize the endometrial tumors associated with adverse outcome and are classified as "high risk". The identification of molecular prognostic factors that might be targeted for therapy among "high risk" endometrial cancers is an active area of investigation. We hypothesize that the FRalpha, highly expressed in endometrial cancer cells, is a potential target for this disease. Our objectives were to determine if FRalpha overexpression is associated with adverse prognostic factors and worse outcome. Three hundred and thirty-two endometrial cancer cores were arrayed onto a tissue microarray and stained using a FRalpha-specific monoclonal antibody. Staining was scored as absent or weak and moderate or strong. Forty-one percent of 310 evaluable cases stained moderate/strong. Moderate/strong FRalpha staining was significantly associated with other poor prognostic factors including: advanced stage, nonendometrioid histology and high grade. An association was observed between moderate/strong FRalpha staining and recurrence (p < 0.0014). These findings support further exploring a role for FRalpha targeted approaches for therapy and diagnostics in endometrial cancer.