Folate receptor alpha as a tumor target in epithelial ovarian cancer

Abstract

Objectives: Folate receptor alpha (FRalpha) 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 FRalpha expression in rare histological subtypes, primary disease versus metastatic foci, and recurrent disease.

Methods: FRalpha 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. FRalpha staining was analyzed in light of disease morphology, stage, grade, debulking status, and time from diagnosis to recurrence and death.

Results: FRalpha 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 FRalpha status detected at diagnosis. Metastatic foci were similar to primary tumors in FRalpha staining. FRalpha status was not associated with time to recurrence or overall survival in either univariate or multivariable analyses.

Conclusion: FRalpha 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 FRalpha 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.

Figures

Fig. 1

Weak, moderate, and strong FRα expression. Shown are representative cores of ovarian cancer tissues on TMAs that were scored with weak (A), moderate (B), and strong (C) FRα expression after immunohistochemistry using FBP343 antibody. Note that the tumor stroma is negative and malignant epithelial cells are largely positive.

Fig. 2

FRα expression in primary and recurrent samples. The frequency of FRα expression in matched tumor samples from an initial diagnostic surgery and subsequent secondary debulking surgery for disease recurrence is shown. Examples of four patients representing each of the expression patterns are shown.

Fig. 3

Kaplan–Meier analyses of recurrence-free and overall survival. Recurrence-free survival (A) and overall survival (B) in patients with FRα-positive (thick line) and FRα-negative (hatched line) ovarian tumors.