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Updated: Aug 8, 2026
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An Immunohistopathologic Study to Profile the Folate Receptor Beta Macrophage and Vascular Immune Microenvironment in Giant Cell Arteritis
Published on: February 8, 2019
Folate Receptor Alpha (FRα/FOLR1) Immunohistochemical Expression Across Molecularly Classified Endometrial Carcinomas
Diane Libert1, Brooke Liang1, Sabrina Zdravkovic1
1Department of Pathology, Stanford University School of Medicine, Stanford, California.
Summary
Folate receptor alpha (FOLR1) expression is low in most endometrial cancers (ECs), but higher in p53-abnormal and no specific molecular profile subtypes. FOLR1 testing may guide treatment for specific EC groups, but retesting at recurrence is advised.
Area of Science:
- Gynecologic Oncology
- Molecular Pathology
- Biomarker Discovery
Background:
- Mirvetuximab soravtansine approval for ovarian cancer highlights folate receptor alpha (FOLR1) as a therapeutic target.
- Characterization of FOLR1 expression in endometrial carcinoma (EC) using standardized assays is lacking.
- Understanding FOLR1 expression patterns is crucial for exploring targeted therapies in EC.
Purpose of the Study:
- To characterize FOLR1 expression across diverse EC histotypes and molecular subtypes.
- To assess the association of FOLR1 expression with clinical biomarkers and survival outcomes.
- To evaluate FOLR1 expression variability in primary versus recurrent tumors and its potential utility in EC.
Main Methods:
- Immunohistochemistry using the VENTANA FOLR1-2.1 assay on 169 molecularly classified EC tissue microarrays.
- Scoring FOLR1 expression by proportion score (PS2 and PS1) using ovarian cancer eligibility criteria and exploratory thresholds.
- Analysis of associations with histotype, TCGA molecular subtype, ER/PR/HER2 status, survival, heterogeneity, and primary-recurrence concordance.
Main Results:
- Only 3% of ECs met the ovarian cancer eligibility threshold (PS2 ≥75), all in p53-abnormal tumors. 9% showed PS2 ≥25, mainly in p53-abnormal and no specific molecular profile (NSMP) subgroups.
- Uterine serous carcinoma exhibited the highest FOLR1 expression; clear cell carcinomas lacked expression. Higher FOLR1 correlated with poorer survival, influenced by molecular subtype and grade.
- FOLR1 expression was homogeneous within cores but showed variability between primary and recurrent tumors.
Conclusions:
- FOLR1 testing in EC appears most relevant for p53-abnormal and NSMP subtypes, and potentially not useful for clear cell carcinomas.
- FOLR1 may have prognostic value in low-grade endometrioid and ER/PR-positive EC.
- Retesting FOLR1 at tumor recurrence is recommended; further trials are needed to evaluate lower expression thresholds for treatment eligibility.
