Synapse - Folate receptor alpha expression in low-grade serous ovarian cancer: Exploring new therapeutic possibilities

Folate receptor alpha expression in low-grade serous ovarian cancer: Exploring new therapeutic possibilities Journal Article

Authors:	Manning-Geist, B. L.; Sullivan, M. W.; Zhou, Q.; Iasonos, A.; Selenica, P.; Stallworth, C.; Liu, Y.; Long Roche, K.; Gordhandas, S.; Aghajanian, C.; Chi, D.; O'Cearbhaill, R.; Grisham, R. N.; Chui, M. H.
Article Title:	Folate receptor alpha expression in low-grade serous ovarian cancer: Exploring new therapeutic possibilities
Abstract:	Objective: Mirvetuximab soravtansine may be a potentially effective therapeutic option for ovarian low-grade serous carcinoma (LGSC), but the prevalence of folate receptor alpha (FRα) overexpression in this tumor type is unknown. We sought to characterize FRα expression in LGSC and its association with clinical and molecular features. Methods: FRα immunohistochemistry was performed on a tissue microarray comprised of 89 LGSCs and 42 ovarian serous borderline tumors (SBTs). Clinical tumor-normal panel-based sequencing was performed on 78 LGSCs. Associations between FRα-high status and clinicopathologic characteristics and survival outcomes were examined. Results: Of 89 LGSCs, 36 (40%) were FRα-high (≥75% of viable tumor cells exhibiting moderate-to-strong membranous expression). Of 9 patients with LGSC and samples from different timepoints, 4 (44%) had discordant results, with conversion from FRα-negative to FRα-high in 3 (33%) cases. There was no association between FRα-high status with age, race, or progression-free/overall survival. A MAPK pathway genetic alteration, most commonly involving KRAS (n = 23), was present in 45 (58%) LGSCs. Those lacking MAPK pathway alterations were more likely to be FRα-high compared to MAPK-altered LGSCs (61% vs 20%, p < 0.001). In SBTs, FRα-high expression was associated with high-risk (micropapillary) histology and/or subsequent LGSC recurrence compared to conventional SBTs without malignant recurrence (53% vs 9%, p = 0.008). Conclusions: Future studies of FRα-directed therapy in patients with LGSC are warranted. Discordant FRα status at recurrence suggests potential benefit for retesting. A biomarker-driven approach to direct treatment selection in LGSC is recommended. As high FRα expression is more common amongst tumors lacking MAPK pathway genetic alterations, FRα testing to determine eligibility for mirvetuximab soravtansine therapy is particularly recommended for this subgroup. © 2024 Elsevier Inc.
Keywords:	ovarian cancer; folate receptor alpha; antibody-drug conjugate; folr1
Journal Title:	Gynecologic Oncology
Volume:	188
ISSN:	0090-8258
Publisher:	Elsevier Inc.
Date Published:	2024-09-01
Start Page:	52
End Page:	57
Language:	English
DOI:	10.1016/j.ygyno.2024.06.008
PROVIDER:	scopus
PUBMED:	38941962
PMCID:	PMC11368654
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-85196801335&doi=10.1016%2fj.ygyno.2024.06.008&partnerID=40&md5=7680dbeb3c059991bb22971ad1c4387c
Notes:	Article -- MSK Cancer Center Support Grant (P30 CA008748) acknowledged in PDF -- MSK Corresponding authors are Rachel Grisham and M. Herman Chui -- Source: Scopus