Reduced folate receptor alpha (FOLR1) protein expression in fallopian tubes from premenopausal women: implications for the FOLR1 CDx assay for mirvetuximab-soravtansine therapy.

Mirvetuximab-soravtansine (MIRV-S) is an antibody-drug conjugate targeting folate receptor alpha (FOLR1). MIRV-S is approved for the treatment of FOLR1-positive, platinum-resistant ovarian carcinoma. Patient eligibility is determined by immunohistochemistry (IHC) using a companion diagnostic (CDx) assay (FOLR1-2.1, Ventana). This assay requires on-slide positive controls (OPCs) to aid FOLR1 evaluation. The manufacturer recommends normal fallopian tube (NFT) tissue for OPCs. Estrogen receptor signaling represses FOLR1 in cell culture models. It is unknown whether hormonal factors, such as menopausal status, also impact on FOLR1 immunoreactivity in NFTs used as OPCs. To address this question, we studied FOLR1 protein expression in NFTs (n = 51) from women aged 26-83 years. IHC was performed with the FOLR1-2.1 CDx assay. Immunoreactivity at apical and basolateral cell membranes was assessed using H-scores (aH-score and bH-score respectively). Overall FOLR1 expression was evaluated using a combined H-score (cH-score; i.e. aH- and bH-scores added together). Immunoreactivity scores in pre-, peri-, and postmenopausal age groups were compared with the chi-square test for trends. NFTs showed variable FOLR1 protein expression [median aH-score: 152.5, interquartile range (IQR): 120-175; median bH-score: 35, IQR: 7-85; median cH-score: 195, IQR: 140-245]. Apical immunoreactivity was age-independent (p = 0.619), but low or absent basolateral immunoreactivity (bH-score <35) was associated with premenopausal age (p = 0.018). Low overall FOLR1 expression (cH-score <195) was also associated with premenopausal age (p = 0.037). In conclusion, NFTs show an age-dependent FOLR1 expression pattern, which likely reflects hormonal repression of FOLR1 in premenopausal women. NFT tissue from postmenopausal women is appropriate and meets the requirements for the current FOLR1 CDx assay.