Testing and Interpretation of Human Epidermal Growth Factor Receptor 2 Protein Expression and ERBB2 Gene Amplification in Advanced Urothelial Carcinoma

作者：Vadim S. Koshkin, Johanna M. Schafer, Emilie Scherrer, Christine Boyiddle, Naomi R. M. Schwartz, Hong Yu, Qijun Fang, Amanda F. Baker, Farzaneh H. Sayedian, Emily Chan · 发表于：JCO Precision Oncology · 年份：2025 · DOI：10.1200/po-24-00879 · 被引用次数：12 · 研究领域：Bladder and Urothelial Cancer Treatments、Urinary and Genital Oncology Studies、Genetic factors in colorectal cancer

PURPOSE The aim of this study was to assess the prevalence of human epidermal growth factor receptor 2 (HER2) protein expression and ERBB2 gene amplification in a large cohort of tumor samples from patients with advanced urothelial carcinoma (UC). MATERIALS AND METHODS Testing was performed on formalin-fixed, paraffin-embedded tissue from commercially sourced primary advanced or metastatic UC using an anti-HER2/neu (4B5) rabbit monoclonal antibody immunohistochemistry (IHC) assay (detects HER2 protein) and HER2 dual in situ hybridization (DISH) DNA probe cocktail assay (detects ERBB2 gene and the centromere of its residing chromosome 17). The HER2 clinical status was classified as HER2-zero (IHC 0), HER2-low (IHC 1+ or IHC 2+/DISH nonamplified), or HER2-positive (IHC 2+/DISH amplified or IHC 3+). RESULTS Of the 2,024 UC samples, HER2 protein expression was IHC 0 for 962 (47.5%), IHC 1+ for 297 (14.7%), IHC 2+ for 498 (24.6%), and IHC 3+ for 267 (13.2%). The percentage of HER2-expressing tumors (IHC 1+, 2+, and 3+) was similar between primary (52.2%, 1,028/1,968) and metastatic UC samples (60.7%, 34/56; P = .26). The ERBB2 gene was amplified in 235 cases (11.6%), including 2.7%/3.7%/9.6%/56.2% scored as IHC 0/1+/2+/3+, respectively. Overall, HER2 clinical status was HER2-zero for 962 UC tissue samples (47.5%; 95% CI, 45.4 to 49.7), HER2-low for 747 (36.9%; 95% CI, 34.8 to 39.0), and HER2-positive for 315 (15.6%; 95% CI, 14.0 to 17.2). CONCLUSION We observed that more than 50% ...