Folate receptor alpha as a tumor target in epithelial ovarian cancer

Objectives. Folate receptor alpha (FR alpha) is a folate-binding protein overexpressed on ovarian and several other epithelial malignancies that can be used as a target for imaging and therapeutic strategies. The goal of this study is to improve historical data that lack specific information about FR alpha expression in rare histological subtypes, primary disease versus metastatic foci, and recurrent disease. Methods. FR alpha expression was analyzed by immunohistochemistry on 186 primary and 27 recurrent ovarian tumors, including 24 pairs of samples obtained from the same individuals at diagnosis and at secondary debulking surgery. For 20 of the 186 primaries, simultaneous metastatic foci were also analyzed. FR alpha staining was analyzed in light of disease morphology, stage, grade, debulking status, and time from diagnosis to recurrence and death. Results. FR alpha expression was apparent in 134 of 186 (72%) primary and 22 of 27 (81.5%) recurrent ovarian tumors. In 21 of 24 (87.5%) matched specimens, recurrent tumors reflected the FR alpha status detected at diagnosis. Metastatic foci were similar to primary tumors in FR alpha staining. FR alpha status was not associated with time to recurrence or overall survival in either univariate or multivariable analyses. Conclusion. FR alpha expression occurs frequently, especially in the common high-grade, high-stage serous tumors that are most likely to recur. New findings from this study show that FR alpha expression is maintained on metastatic foci and recurrent tumors, suggesting that novel folate-targeted therapies may hold promise for the majority of women with either newly diagnosed or recurrent ovarian cancer. (C) 2007 Elsevier Inc. All rights reserved.