Folate receptor alpha expression in uterine serous carcinoma: a single-institution analysis

Uterine serous carcinoma (USC) is an aggressive histologic subtype of endometrial cancer for which limited targeted therapeutic options exist. Folate receptor alpha (FOLRα) is an established therapeutic target in high-grade serous ovarian carcinoma, but its expression patterns in USC remain poorly characterized. We sought to evaluate the prevalence and distribution of FOLRα expression in USC and assess the applicability of ovarian cancer-derived FOLRα thresholds to this histology. We conducted a retrospective review of patients with pathologically confirmed USC treated at a single institution from 2017 to 2024. FOLRα expression was assessed using the VENTANA FOLR1 (FOLR1-2.1) RxDx assay. Positivity was defined as ≥75% of tumor cells demonstrating moderate-to-strong membranous staining (PS2+ scoring). Seventy-three patients were included. Median age was 71 years; 53% had uterine-confined disease at presentation. In our cohort, nine tumors (12.3%) met the high-expression threshold for FOLRα positivity. An additional 13 tumors (17.8%) demonstrated intermediate expression, while 69.9% showed <50% staining. FOLRα expression in USC is variable, and only a minority of tumors met the high-expression threshold used for mirvetuximab soravtansine (MIRV) eligibility in ovarian cancer. However, nearly one-third demonstrated medium-to-high expression, suggesting that FOLRα targeting may not be fully captured by ovarian cancer-derived biomarker cutoffs in this disease process. These descriptive, hypothesis-generating findings support further evaluation of FOLRα-directed strategies, including combination approaches, in prospective studies of USC.