Heterogeneity of folate receptor alpha expression and associations with molecular biomarker in ovarian high-grade serous carcinoma: A multicenter Chinese cohort study.

Background

Folate receptor alpha (FRα) is an established therapeutic target in ovarian cancer, but information on its expression distribution, staining heterogeneity, and molecular context in Chinese patients remains limited. We evaluated these features in ovarian high grade serous carcinoma (HGSC).

Methods

This retrospective multicenter study included 1002 patients with resected HGSC from 14 Chinese hospitals. FRα expression was assessed using the VENTANA FOLR1 (FOLR1-2.1) RxDx Assay based on the percentage of viable tumor cells with moderate or strong (2+/3+) membranous staining. Intensity specific percentages were available for 992 tumors. Associations with clinicopathologic features and BRCA1/2, HRD, TMB, MSI, MMR, HER2, and PD-L1 were exploratory. Temporal concordance was evaluated in 53 paired primary and recurrent tumors.

Results

High FRα expression, defined as 2+/3+ staining in ≥75% of viable tumor cells, was observed in 435 of 1002 tumors (43.41%). Among 992 tumors with intensity data, 972 (98.0%) contained at least two staining categories, and 924 (93.1%) contained both negative or weak and moderate or strong tumor cell populations. No significant associations were detected with age, FIGO stage, tumor size, or the biomarkers evaluated, although analyses were limited and underpowered. Paired tumors showed 71.7% categorical agreement (Cohen's κ = 0.44) and moderate correlation of FRα percentages (Spearman ρ = 0.59).

Conclusions

FRα expression showed substantial variation between tumors and frequent intensity admixture within specimens. Biomarker associations remain inconclusive because of limited testing. Moderate primary and recurrent concordance supports archival testing, while discordance suggests repeat testing at recurrence may be appropriate in selected patients.