FRα expression in borderline ovarian tumors and low-grade serous ovarian carcinoma: prognostic and immune microenvironmental associations.

Abstract

Background: Folate receptor alpha (FRα) is overexpressed in various epithelial ovarian carcinomas and has emerged as a potential therapeutic target. However, its expression pattern and clinical significance in borderline ovarian tumors (BOTs) and related low-grade serous tumors remain unclear. This study aimed to investigate the association between FRα expression and clinicopathologic characteristics of BOTs and low-grade serous ovarian carcinomas (LGSOC), and to explore the features of the tumor immune microenvironment in relation to FRα expression.

Results: A total of 100 surgically resected ovarian epithelial tumors (2014-2024) were retrospectively analyzed, including 91 BOTs and 9 LGSOCs. FRα expression was heterogeneous across histologic subtypes. High FRα expression (immunoreactive score ≥ 8) was detected in 13% (13/100) of cases and was predominantly observed in serous tumors (15.6%, 12/77). Within the serous subset, tumors with micropapillary features showed higher FRα expression, approaching levels observed in LGSOCs. FRα-high cases demonstrated a significantly higher recurrence rate compared with FRα-low tumors (42% vs. 14%, P = 0.003), particularly in serous subset. FRα expression was inversely correlated with immune cell infiltration and positively correlated with PD-L1 (r = 0.36, P < 0.001) and PD-1 expression. Moreover, a high proportion of FRα⁺PD-L1⁺ double-positive tumor epithelial cells in serous tumors was associated with shorter disease-free survival.

Conclusions: FRα expression was heterogeneous across BOT subtypes and tended to be higher in SBOTs with micropapillary features and LGSOCs. High FRα expression is associated with tumor recurrence and an immunosuppressive microenvironment, suggesting that FRα may serve as a prognostic biomarker and a potential therapeutic target in BOTs and LGSOCs.