Her-2 Overexpression in Female Genital Tract Clear Cell Carcinomas: Evaluation of Different Scoring Guidelines, Clinicopathological Features and Prognostic Impact Publisher Pubmed



Edjtemaei R¹ ; Nili F¹ ; Jahanzad I¹ ; Ameli F¹ ; Ghasemi D¹ Show Affiliations
Source: Annals of Diagnostic Pathology Published:2023

Abstract

Background: Clear cell carcinoma (CCC) is a rare high-grade adenocarcinoma associated with poor response to platinum-based chemotherapy agents in the female genital tract. Human epidermal growth factor receptor 2 (HER2) overexpression is routinely used as a biomarker for targeted therapy in breast and gastric carcinomas, but its role in CCC remains unclear. Methods: In this study, HER2 overexpression was evaluated by immunohistochemistry (IHC) using College of American Pathologists (CAP) HER2 scoring guidelines for breast and endometrial serous carcinoma (ESC) on tissue microarray blocks. In equivocal and positive cases, fluorescence in situ hybridization (FISH) was performed. IHC score 3, and all amplified cases on FISH test were considered positive. Results: Thirty-six cases of ovarian (OCCC), 36 endometrial (ECCC), and 2 cervical CCC were included. According to ESC and breast scoring guidelines, 20 % and 15.1 % of ECCC and 14.7 % and 6 % of OCCC were HER2 positive, respectively. Both cases of cervical CCC were negative. Scoring based on breast carcinoma guideline showed higher concordance (100 %) with gene amplification results, in comparison with ESC guideline (82.7 %). On multivariate survival analysis, HER2 positive ECCC and OCCC (based on ESC scoring methods) had significantly lower overall and disease-free survivals (OS, DFS) (P < 0.05). Conclusion: HER2 immunoscoring based on ESC guideline can yield a higher sensitivity with relevant clinical and prognostic features in OCCC and ECCC. HER2 can be considered a potential biomarker for targeted therapy and future clinical trials. © 2023 Elsevier Inc.