Folate receptor alpha (FRα/FOLR1) and HER2 immunohistochemical staining in high‐grade endometrial carcinoma with aberrant p53 expression

Aims Mirvetuximab soravtansine is an anti‐FOLR1 (folate receptor 1/alpha) antibody–drug conjugate with a companion diagnostic immunohistochemical (IHC) biomarker for platinum‐resistant ovarian, fallopian tube and primary peritoneal carcinoma. Its effectiveness has sparked interest in FOLR1 expression in endometrial carcinoma. We evaluate the relationship of FOLR1 and HER2‐IHC expression in high‐grade p53‐aberrantly expressed endometrial carcinomas, as overexpression of both is associated with high‐grade histologic features and aggressiveness. Methods and results Carcinomas were scored for HER2‐IHC by both gastric and endometrial serous criteria and FOLR1‐IHC by Ventana package insert on tissue microarray cores. Intratumoral heterogeneity was quantified for HER2 and FOLR1 expression across multiple cores from the same tumour. A total of 291 cores (226 endometrial serous, 47 high‐grade endometrioid and 18 high‐grade Müllerian carcinoma, nos) were collected from 66 cases (discrete accession dates) from 62 patients. When stratified by two‐category HER2‐IHC status (0/1+ vs. 2+/3+, either criteria), significantly more HER2 2+/3+ cores (16/133, 12%) were FOLR1‐positive by a ≥75% cut‐off than HER2 0/1+ specimens (8/158, 5%, P = 0.031). Results were similar by a ≥25% cut‐off (49/133, 37% vs. 38/158, 24%; P = 0.018). More cases with high HER2‐IHC heterogeneity (2–3‐pt difference) also demonstrated FOLR1‐IHC heterogeneity (≥50% score difference between cores from the same case) than cases with no or low (1‐pt) HER2‐IHC heterogeneity, though most cases did not show high HER2 or FOLR1 intratumoral heterogeneity (16.7%–18.2% 2–3‐pt difference and 12.1% ≥50% score difference). Conclusions A positive correlation between HER2 and FOLR1 overexpression may be seen in high‐grade endometrial carcinomas with aberrant p53 expression, which may extend to intratumoral heterogeneity of biomarker expression.