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Molecular and Clinicopathologic Features Associated With FOLR1 Expression in Gynecologic Malignancies.
Rachelle P Mendoza1, Marie C Smithgall, Xiaowei Chen
1Department of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, New York.
Summary
Folate receptor 1 (FOLR1) is expressed in 10.1% of gynecologic tumors, particularly high-grade serous ovarian cancers. FOLR1 overexpression correlates with poor prognostic factors and specific genetic mutations, indicating its potential as a therapeutic target.
Area of Science:
- Gynecologic Oncology
- Cancer Biomarkers
- Molecular Pathology
Background:
- Folate receptor 1 (FOLR1) is an emerging therapeutic target for advanced cancers.
- Understanding FOLR1 expression prevalence and its clinical correlations in gynecologic tumors is crucial.
Purpose of the Study:
- To investigate the prevalence of FOLR1 expression in various gynecologic tumors.
- To correlate FOLR1 expression with clinicopathologic features and molecular alterations.
Main Methods:
- Immunohistochemistry (IHC) was used to evaluate FOLR1 expression in 306 gynecologic tumors.
- Positive FOLR1 defined as ≥75% tumor cells with moderate to strong membrane staining.
- Statistical analysis correlated FOLR1 status with clinicopathologic and molecular data.
Main Results:
- FOLR1 was expressed in 10.1% of tumors, predominantly in high-grade serous ovarian cancers (64.5%).
- FOLR1 overexpression correlated with positive PD-L1, intact MMR, and positive ER expression.
- In endometrial tumors, FOLR1 positivity associated with poor grade, larger size, mutant p53, and lower PR; TP53 mutations were higher, PTEN alterations absent.
- FOLR1 overexpression linked to adverse prognostic factors including advanced stage, recurrence, higher T/N stage, poor grade, larger size, lymphovascular invasion, serosa involvement, and shorter progression-free survival.
Conclusions:
- FOLR1 is a significant biomarker in gynecologic cancers, especially HGSCs.
- FOLR1 overexpression is associated with aggressive tumor behavior and poor prognosis.
- Targeting FOLR1 may offer a therapeutic strategy for a subset of gynecologic cancer patients.
