Site Editor
Joyce F. Liu, MD, MPH
Joyce F. Liu, MD, MPH
Posted: Wednesday, February 5, 2025
Folate receptor-alpha (FOLR1) expression may be a viable therapeutic target for low-grade serous ovarian carcinoma (LGSOC), according to a study conducted by Tullia Rushton, MD, of Johns Hopkins Hospital, Baltimore, and colleagues. Although FOLR1 has been widely studied in high-grade serous ovarian carcinoma (HGSOC) and is now a U.S. Food and Drug Administration–approved target for antibody-drug conjugates such as mirvetuximab soravtansine-gynx, a substantial portion of LGSOC tumors were found also to exhibit FOLR1 positivity. The findings of this commercial database study were published in the journal Gynecologic Oncology.
“Our study demonstrates that one-quarter of patients with low-grade serous ovarian carcinoma express strong FOLR1 positivity, with a greater frequency observed in patients without BRAF or NRAS mutations,” stated the study investigators.
This observational study included 281 samples of LGSOC and 5,086 sample of HGSOC from a molecular oncology database. FOLR1 expression was measured using immunohistochemistry and transcriptomic profiling. Molecular alterations were analyzed using next-generation sequencing and whole-exome sequencing, and immune markers and pathway activations were assessed via RNA sequencing.
The study found that 24.6% of LGSOC tumors exhibited high FOLR1 expression (≥ 75% moderate/strong staining intensity), compared with 43.5% of HGSOC tumors. KRAS and NRAS mutations as well as MAPK pathway activation was significantly higher in low-grade than in high-grade serous ovarian carcinomas, irrespective of FOLR1 status. Of note, BRAF mutations were predominantly found in FOLR1-negative LGSOC. FOLR1-positive HGSOC was associated with a longer median survival (98.1 months vs 86.8 months for FOLR1-negative HGSOC, P = .045), although survival differences were not observed in LGSOC. These findings underscore the potential for FOLR1-targeted therapies in both high- and low-grade serous ovarian carcinomas.
Disclosure: The study authors reported no conflicts of interest.
