Molecular and Clinicopathologic Features Associated With FOLR1 Expression in Gynecologic Malignancies

Folate receptor 1 (FOLR1) has recently become a well-accepted therapeutic target in advanced-stage cancers. In this study, the prevalence of FOLR1 expression across all types of gynecologic tumors was investigated and correlated with selected clinicopathologic features. A total of 306 gynecologic tumors from 304 patients were evaluated for FOLR1 expression by immunohistochemistry (IHC). A positive FOLR1 is defined as ≥75% of viable tumor cells with moderate to strong membrane staining. Of 306 tumors, 31 (10.1%) had positive FOLR1 tests; a large majority of these FOLR1-positive tumors were HGSCs (64.5%), followed by uterine serous carcinoma, poorly differentiated/high-grade carcinoma, ovarian endometrioid carcinoma, ovarian mixed carcinoma, ovarian low-grade serous carcinoma, and serous borderline tumor with cribriform and micropapillary features. FOLR1 overexpression correlated with positive PD-L1 expression ( P =0.012), intact mismatch repair protein (MMR) expression ( P =0.024), and positive ER expression ( P =0.040). In endometrial tumors, positive FOLR1 expression was associated with poor histologic grade ( P =0.019), larger tumor size ( P =0.048), mutant p53 expression ( P <0.001), and lower PR expression ( P =0.015). Endometrial tumors with FOLR1 overexpression had a significantly higher rate of TP53 mutations ( P =0.013), while all endometrial tumors with PTEN alterations were negative for FOLR1 ( P =0.037). Overall, FOLR1 overexpression was associated with poor prognostic factors, such as advanced clinical stage, increased recurrence rate, higher pathologic T and N stage, poor histologic grade, larger tumor size, lymphovascular invasion, uterine serosa involvement, and shorter progression-free survival.