Folate Receptor Immunohistochemical Staining Heterogeneity in Gynecologic Cancers

Mirvetuximab soravtansine is an antibody-drug conjugate targeting FRα, which has not only shown antitumor activity and tolerability in ovarian carcinoma with FRα high expression, but has also been incorporated into NCCN guidelines to treat patients with platinum-resistant disease. Sequential cases were retrieved from a previously published cohort of gynecologic pathology cases in which FOLR1 immunohistochemistry had been performed at our institution. Clinical and pathologic data collected included patients' age, tumor histotype, tumor grade (if reported or relevant to histotype), primary tumor site, FIGO stage, and type of specimen. FOLR1 immunohistochemical results were collected from the report, including the overall tumor percentage and intensity reported, and subsequently determined if this was an overall positive or negative result (positivity defined as per current recommendations for therapy eligibility, 75%, 2-3+ intensity). The FOLR1 immunohistochemical slide was reviewed by 2 gynecologic pathologists and jointly recorded the following parameters: percent of cells staining at each level of intensity (0-3), range of staining intensity (0-3), percent of cells with membranous, cytoplasmic, or mixed staining, apical-only versus any membranous staining, percent of cells with complete membranous staining, and presence of abrupt transition (0 - no staining at all, juxtaposed to 2-3+ staining). One hundred twenty cases were reviewed and scored, 119 of which had original reported scores available for comparison. The staining intensity record was 0 in 9 (7.5%) of the cases, 0-1 in 3 (2.5%), 0-2 in 11 (9.2%), 0-3 in 88 (73.3%), 1-3 in 3 (2.5%), 2-3 in 4 (3.3%), and 3 in 2 (1.7%). The percent of positive cells at 2-3+ intensity as per quartile of cases was 12 (10.0%) cases with 0%, 14 (11.7%) cases with 1%-24%, 15 (12.5%) with 25%-49%, 28 (23.3%) with 50%-74%, and 51 (42.5%) with ≥75%. Using the original clinical reports, 67 (56.3%) of 119 cases were positive; 55 (67.9%) of 81 resection cases were positive, while 12 (31.6%) of 38 biopsy cases were positive. On re-review, 51 (42.5%) of all 120 cases were positive, with 41 (50%) of 82 resection cases being positive and 10 (26.3%) of 38 biopsy cases being positive. Overall, 18 (15.1%) of 119 cases had a clinically significant change (i.e. positive to negative or negative to positive). When broken down by type of specimen, 16 (19.8%) of 81 resection cases had a significant change, while only 2 (5.3%) of 38 biopsy cases had a significant change. Of the original scores taken from the report, the score was clearly stated in 117 reports, of which 47 cases were reported within 65% to 85% 2-3+ intensity. Seventeen of these 47 on rescoring were changed significantly as to a clinical action outcome; all 17 of these were changed from "positive" to "negative." The 18th case, which was changed on rescoring, was the singular case that was changed from "negative" to "positive," which was originally reported at 60% and on review was scored 75%. On rescoring of all 120 cases, 32 cases were 65% to 85% 2-3+ intensity. The heterogeneous staining pattern of FRα expression may lead to difficulties in scoring and interpretation, which can have an impact on clinical management.