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Updated: Aug 8, 2026
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.
Abstract:
The approval of Mirvetuximab soravtansine, a folate receptor alpha (FOLR1)-targeting antibody-drug conjugate, for platinum-resistant ovarian cancer, has prompted interest in FOLR1 as a target in endometrial carcinoma (EC). Characterization of FOLR1 expression across EC histotypes, TCGA molecular subtypes, and clinically relevant biomarkers using the FDA-approved companion diagnostic assay has not been performed. FOLR1 immunohistochemistry was performed on tissue microarrays from 169 molecularly classified ECs using the VENTANA FOLR1-2.1 assay and scored by proportion score PS2 and PS1 criteria at the ovarian cancer eligibility cutoff (PS2 ≥75) as well as exploratory thresholds. Associations with histotype, molecular subtype, biomarker (ER, PR, HER2) status, survival outcomes, intratumoral heterogeneity, and matched primary-recurrence expression were assessed. Only 3% (5/169) of ECs met the PS2 ≥75 threshold; all 5 were p53-abnormal (p53abn). In all, 9% (15/169) showed PS2 ≥25, predominantly in p53abn and no specific molecular profile (NSMP) subgroups. Uterine serous carcinoma had the highest expression; FOLR1 was absent in 3/3 clear cell carcinomas. Higher FOLR1 expression was associated with inferior survival, though this largely reflected molecular subtype and grade. FOLR1 was homogeneous across cores but variable between primary and recurrent tumors. FOLR1 testing in EC may be most relevant in p53abn and NSMP tumors and may not be useful in clear cell carcinomas. FOLR1 may have prognostic value in low-grade endometrioid and ER/PR-positive EC. Retesting at tumor recurrence is recommended. Given the frequency of lower-level FOLR1 expression, trials with treatment-response data are needed to test eligibility criteria below the current ovarian cancer threshold.
Insights
Folate receptor alpha (FOLR1) expression in endometrial cancer (EC) is low, mainly in p53-abnormal subtypes. FOLR1 testing may guide treatment for specific ECs, but retesting at recurrence is crucial.
Area of Science:
- Gynecologic Oncology
- Molecular Pathology
- Translational Cancer Research
Background:
- Mirvetuximab soravtansine approval for ovarian cancer highlights folate receptor alpha (FOLR1) as a therapeutic target.
- FOLR1 expression characterization is needed across endometrial carcinoma (EC) subtypes and molecular profiles.
Purpose of the Study:
- To characterize FOLR1 expression in endometrial carcinoma (EC).
- To assess associations between FOLR1 expression and EC histotype, molecular subtype, biomarkers, and survival.
- To evaluate FOLR1 heterogeneity and expression changes from primary to recurrent tumors.
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) at ovarian cancer eligibility thresholds and exploratory levels.
- Analysis of associations with histotype, TCGA molecular subtype, ER/PR/HER2 status, survival, heterogeneity, and primary-recurrence pairs.
Main Results:
- Only 3% of ECs met the ovarian cancer eligibility threshold (PS2 ≥75), all in p53-abnormal tumors.
- 9% of ECs showed PS2 ≥25, predominantly in p53-abnormal and no specific molecular profile (NSMP) subgroups.
- Uterine serous carcinoma exhibited the highest FOLR1 expression; clear cell carcinomas lacked FOLR1. Higher expression correlated with inferior survival, influenced by subtype and grade. Expression was homogeneous within cores but variable between primary and recurrent tumors.
Conclusions:
- FOLR1 expression is generally low in EC, with higher levels in p53-abnormal and NSMP subtypes.
- FOLR1 testing may be most relevant for p53-abnormal and NSMP ECs, but not for clear cell carcinomas.
- FOLR1 may have prognostic value in low-grade endometrioid and ER/PR-positive EC. Retesting at recurrence is recommended, and further trials are needed for lower expression thresholds.
