Histopathological spectrum of endometrial lesions and association of HER2/neu expression with aggressive clinicopathological features in endometrial carcinoma

Background: The successful introduction of HER2/neu-targeted therapies in breast cancer has prompted investigation into their potential application in endometrial carcinoma. However, standardized criteria for evaluating HER2/neu status in endometrial cancer are not yet fully established, and its prognostic role requires further elucidation.Objectives: This study aimed to determine the histopathologic spectrum of endometrial lesions in patients presenting with abnormal uterine bleeding and to evaluate the expression of HER2/neu (human epidermal growth factor receptor 2) in endometrial carcinoma, correlating it with key clinicopathological parameters to assess its prognostic significance.Methods: We conducted a prospective observational study of 350 endometrial biopsy and hysterectomy specimens. Histological analysis was performed on all specimens. HER2/neu expression was assessed via immunohistochemistry in hysterectomy specimens diagnosed with carcinoma, using the 2018 American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) scoring guidelines.Results: The most common histopathological finding was proliferative phase endometrium (18.86%). Among the 16 cases of endometrial carcinoma analyzed for HER2/neu expression, 3+ overexpression was observed in 4 cases (25.0%), 2+ (equivocal) in 2 cases (12.5%), 1+ in 5 cases (31.25%), and 0 (negative) in 5 cases (31.25%). HER2/neu 3+ overexpression was significantly associated with advanced FIGO stage (P = 0.001) and deeper myometrial invasion (P = 0.015). This overexpression was significantly more frequent in non-endometrioid (100% of serous carcinomas) compared to endometrioid histologies (14.28%; P = 0.008) and was strongly correlated with high tumor grade (Grade 3; P = 0.0004).Conclusion: Our findings indicate that overexpression of HER2/neu (3+) is significantly associated with aggressive tumor characteristics, including non-endometrioid histology, myometrial invasion, advanced stage, and high tumor grade. These results support the potential utility of HER2/neu as a prognostic biomarker and a candidate for targeted therapy in a distinct subset of high-risk endometrial carcinomas.