Folate Receptor Immunohistochemical Staining Heterogeneity in Gynecologic Cancers

Area of Science:

• Gynecologic Pathology
• Oncology
• Immunohistochemistry

Background:

• Mirvetuximab soravtansine targets folate receptor alpha (FRα) and is used for ovarian cancer with high FRα expression.
• Accurate FRα assessment is crucial for patient eligibility for FRα-targeted therapies.
• Heterogeneous FRα expression can complicate immunohistochemical scoring.

Purpose of the Study:

• To assess the reliability of FRα immunohistochemical scoring in a cohort of gynecologic pathology cases.
• To identify discrepancies between original clinical reports and expert re-review of FRα staining.
• To evaluate the clinical significance of scoring changes for FRα-targeted therapy eligibility.

Main Methods:

• Retrospective review of 120 gynecologic pathology cases with prior FOLR1 immunohistochemistry.
• Collection of clinical and pathological data, including patient demographics, tumor characteristics, and FIGO stage.
• Standardized re-evaluation of FRα staining by two gynecologic pathologists, assessing intensity, percentage of positive cells, and staining patterns.
• Comparison of original reported scores with re-review scores to identify significant changes.

Main Results:

• Original reports classified 56.3% of 119 cases as FRα positive, while re-review found 42.5% of 120 cases positive.
• A clinically significant change in FRα status (positive to negative or vice versa) occurred in 15.1% of cases.
• Resection specimens showed a higher rate of significant scoring changes (19.8%) compared to biopsy specimens (5.3%).
• Seventeen cases initially reported as positive were reclassified as negative, impacting potential treatment eligibility.

Conclusions:

• Significant discordance exists between initial FRα scoring and expert re-evaluation, particularly in resection specimens.
• Heterogeneous FRα expression patterns contribute to scoring difficulties and potential misinterpretation.
• Standardized scoring criteria and pathologist expertise are essential to ensure accurate FRα assessment for guiding targeted therapy decisions in ovarian cancer.