Mitra Abdollahi Neisani, Francis E Marrero, Roberto Angeli-Morales, Sinan G Khudhur, Kevin J Wu, Yaohua Ma, Sophia G Blumenfeld, Karina Hanna, Gerardo Colon-Otero, Aziza Nassar
FRα expression in ovarian carcinomas is generally stable over time, with concordance observed in most paired specimens. However, discordance in approximately one-quarter of cases suggests spatial and/or temporal tumor heterogeneity.
BACKGROUND: Folate receptor alpha (FRα) is frequently expressed in ovarian high-grade serous carcinomas and is a clinically actionable biomarker targeted by FDA-approved mirvetuximab soravtansine (MIRV) for platinum-resistant disease with high expression (≥75% of tumor cells with ≥2+ staining). However, longitudinal variability in FRα expression remains poorly understood. We evaluated temporal FRα expression changes in paired ovarian cancer specimens.
METHODS: We performed a retrospective study of epithelial ovarian malignancies at Mayo Clinic Florida (2013-2025) in patients with ≥2 tumor specimens available. Tumors were classified as FRα-positive when ≥75% of viable tumor cells showed moderate-to-strong (2+ and/or 3+) staining and categorized as concordant or discordant based on changes in FRα status. Associations between clinicopathologic variables and FRα variability were evaluated using Fisher exact and Kruskal-Wallis tests.
RESULTS: Sixty-six patients (median age 66 years), most with advanced-stage high-grade serous carcinoma (65/66), had paired tumor specimens. FRα expression was concordant in 77.3% of cases and discordant in 22.7%. Negative-to-positive conversion occurred more frequently than positive-to-negative conversion (16.7% vs 6.1%). No significant associations were identified between FRα variability and clinicopathologic factors, including age, grade, stage, treatment setting, prior chemotherapy exposure, MIRV use, specimen type, sampling site, baseline FRα expression, or timing intervals. In patients treated with neoadjuvant chemotherapy, negative-to-positive conversion was numerically more frequent, although not statistically significant (25% vs 9%; p = 0.479).
CONCLUSIONS: FRα expression in ovarian carcinomas is generally stable over time, with concordance observed in most paired specimens. However, discordance in approximately one-quarter of cases suggests spatial and/or temporal tumor heterogeneity.