The effect of chemotherapy on expression of folate receptor-alpha in ovarian cancer

Lucia M A Crane, Henriette J G Arts, Marleen van Oosten, Philip S Low, Ate G J van der Zee, Gooitzen M van Dam, Joost Bart, Lucia M A Crane, Henriette J G Arts, Marleen van Oosten, Philip S Low, Ate G J van der Zee, Gooitzen M van Dam, Joost Bart

Abstract

Background: Folate receptor alpha (FR-α) has been identified as a potential target in ovarian cancer for diagnostic and therapeutic purposes, based on its overexpression in serous epithelial ovarian carcinoma. The effect of chemotherapy on FR-α expression may be important in the applicability of FR-α directed agents in the case of residual tumor tissue. The objective of this study was to assess FR-α expression in ovarian carcinoma and to evaluate whether FR-α expression is altered by chemotherapy.

Materials & methods: FR-α expression was analyzed by semi-quantitative scoring of immunohistochemical staining on tissue microarrays (TMAs) from a database containing 361 ovarian cancer tissue samples, of which 210 serous and 116 non-serous carcinoma (35 missing). Serous carcinoma samples included 28 matched samples with tissue from both primary surgery and interval debulking surgery, and 12 matched samples with tissue from both primary surgery and surgery for recurrent disease.

Results: FR-α expression was seen in 81.8% of serous ovarian cancers versus 39.9% of non-serous carcinomas (p < 0.001). In matched serous carcinoma samples, no significant change in FR-α expression in vital tumor tissue after chemotherapy was observed (p = 0.1). FR-α expression was not a prognostic marker of progression free survival (p = 0.8) or overall survival (p = 0.7).

Conclusion: FR-α was expressed in the majority of serous ovarian tumors, although >50% of cases showed only weak expression. Chemotherapy did not alter expression rates in remaining vital tumor tissue, indicating that folate-targeted agents may have a place in the treatment for ovarian cancer, before as well as after chemotherapy. Furthermore, FR-α status did not influence survival.

Figures

Fig. 1
Fig. 1
FR-α expression in representative samples a—no expression (0); b—weak expression (1); c—moderate expression (2); d—strong expression (3)
Fig. 2
Fig. 2
FR-α expression pre- and post-chemotherapy. Left column: pre-chemotherapy. Right column: post-chemotherapy. a—negative/negative. b—negative/positive. c—positive/negative. d—positive/positive
Fig. 3
Fig. 3
Survival curves for serous tumors a—Overall survival (follow-up in months); p = 0.7 b—Progression free survival in months; p = 0.8

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