Histopathology · 2025
Folate receptor alpha (FRα/FOLR1) and HER2 immunohistochemical staining in high-grade endometrial carcinoma with aberrant p53 expression.
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McHenry Austin, Liang Brooke, Libert Diane, Hammer Phoebe M, Tokuyama Minami, Tenney Troy, Zhang Xiaoming, Folkins Ann, Longacre Teri A, Howitt Brooke E
Аннотация
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.
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.