Follicle-Stimulating Hormone Receptor Expression and Its Potential Application for Theranostics in Subtypes of Ovarian Tumors: A Systematic Review

Abstract

Ovarian cancer mortality rates have not decreased significantly in the past years. As most women are still diagnosed in an advanced stage, there is a need for new treatment strategies for recurrent disease. A potentially new developing targeted approach, theranostics, combines diagnostics and treatment using radiopharmaceuticals. Through target receptors, imaging and treatment of malignant tissue can be achieved. For ovarian malignancy, the follicle-stimulating hormone (FSH) receptor may serve as a possible target since expression appears to be limited to ovarian cells. In this systematic review, we aim to gather all available literature on the expression of the FSH receptor in ovarian tumors. Pubmed, Embase and the Cochrane databases were searched until December 2023 for eligible studies. The search yielded 41 studies, mostly regarding serous carcinomas, sex cord-stromal tumors (SCSTs) and cell lines of serous and SCSTs. Various techniques were used to analyze the expression of the FSH receptor. For serous carcinomas, conflicting results on the expression of the FSH receptor were found. Studies on SCSTs, mainly studying the subtype of granulosa cell tumors, all showed positive expression of the FSH receptor. In the cell lines studies, the KGN cell line derived from a granulosa cell tumor shows positive expression in all studies. Available studies show that SCSTs express the FSH receptor. A theranostic approach targeting the FSH receptor may, therefore, provide a useful new approach for this malignancy with limited therapeutic options in recurrent disease.

Keywords: FSH receptor; ovarian cancer; theranostics.

Figure 3

FSH receptor expression in subtypes of ovarian tumors, visualized by two outcomes: detection of FSH receptor by yes or no (left Y-axis, bar graph) and mean percentage of tumors expressing the FSH receptor using IHC (right Y-axis, triangular points). FSHR: follicle-stimulating hormone receptor; SCST: sex cord–stromal tumor; IHC: immunohistochemistry. * Immunoreactive score (IRS) > 3.

Figure 1

Flowchart of FSH receptor literature search (PRISMA flow diagram template 2020).

Figure 2

All types of ovarian tumors analyzed by various methods to detect FSH receptor expression. (A) Distribution of type of ovarian tumors examined by included studies (n = 41); (B) different techniques to examine the FSH receptor, distributed per type of ovarian tumor. SCST: sex cord–stromal tumor; RT: reversed transcriptase; PCR: polymerase chain reaction; ISH: in situ hybridization; iFSH: Iodium-labeled FSH.

Figure 4

FSH receptor expression analyzed in ovarian tumor cell lines. (A) Studies examining FSH receptor in tumor cell lines (n = 23); (B) FSH receptor expression in four most examined ovarian tumor cell lines (SKOV-3, OVCAR-3, CAOV-3 and KGN) examined by various analyzing methods: immunofluorescence, [¹²⁵I]-FSH-binding radioreceptor assay, cAMP assay, flow cytometry, RT-PCR, ICC and Immunoblot. * Low expression. ICC: immunocytochemistry; RT-PCR: reverse transcriptase polymerase chain reaction.