Prognostic Value of HER2 Protein Expression in Endometrial Cancer: A Study of 98 Cases in the "Souss-Massa Region"

Background: Endometrial cancer is the most common gynecological malignancy in industrialized countries. Among its subtypes, type II tumors (mainly serous and clear cell carcinomas) are associated with poor prognosis. HER2 (ERBB2) overexpression and amplification have been reported as markers of tumor aggressiveness and may represent potential therapeutic targets. Objective: To evaluate the expression of HER2 in endometrial carcinomas and to analyze its association with conventional histopathological prognostic factors. Methods: We conducted a retrospective study including 98 cases of endometrial carcinoma collected in the Souss Massa region (Morocco) between January 2017 and June 2025. Histological type, tumor grade, vascular emboli, myometrial invasion, and parametrial invasion were assessed. HER2 expression was evaluated by immunohistochemistry (IHC) and classified according to a semi-quantitative scoring system (0–3+). Equivocal cases (2+) underwent in situ hybridization (ISH) to assess ERBB2 amplification. Results: The mean age of the patients was 64 ± 6.5 years. Histologically, the cohort included 43 low-grade endometrioid adenocarcinomas, 30 high-grade endometrioid adenocarcinomas, 18 serous carcinomas, 4 carcinosarcomas, and 3 clear cell carcinomas. HER2 overexpression (score 3) was observed in 19 cases (19.4%), mainly in serous carcinomas (78.9%), with smaller proportions in high-grade endometrioid adenocarcinomas (15.8%) and clear cell carcinoma (5.3%). All HER2-positive cases were of high grade, with vascular emboli in 63%, universal myometrial invasion (100%), and parametrial invasion in 37%. In contrast, HER2-negative tumors (80.6%) were predominantly low-grade endometrioid carcinomas, with lower rates of myometrial (31.6%) and parametrial (2.5%) invasion. Conclusion: HER2 overexpression in endometrial carcinoma is strongly associated with aggressive histological subtypes and adverse prognostic features. These findings reinforce the prognostic value of H