Koshkin Vadim S, Schafer Johanna M, Scherrer Emilie, Boyiddle Christine, Schwartz Naomi R M, Yu Hong, Fang Qijun, Baker Amanda F, Sayedian Farzaneh H, Chan Emily
Division of Hematology/Oncology, Department of Medicine, University of California San Francisco, Helen Diller Family Comprehensive Cancer Center, San Francisco, CA.
Roche Diagnostics Solutions, Tucson, AZ.
JCO Precis Oncol. 2025 Apr;9:e2400879. doi: 10.1200/PO-24-00879. Epub 2025 Apr 16.
The aim of this study was to assess the prevalence of human epidermal growth factor receptor 2 (HER2) protein expression and gene amplification in a large cohort of tumor samples from patients with advanced urothelial carcinoma (UC).
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 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+).
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; = .26). The 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).
We observed that more than 50% of 2,024 advanced UC tumors demonstrated some degree of HER2 protein expression detected using a standardized IHC method, whereas about 12% of specimens had gene amplification, including about 3% of those scored as either IHC 0 or 1+. Continued development of optimized and standardized HER2 testing methods is warranted to identify patients with HER2-expressing UC who may benefit from novel HER2-targeting therapies.
本研究旨在评估晚期尿路上皮癌（UC）患者的一大组肿瘤样本中人表皮生长因子受体2（HER2）蛋白表达和基因扩增的患病率。
使用抗HER2/neu（4B5）兔单克隆抗体免疫组织化学（IHC）检测法（检测HER2蛋白）和HER2双重原位杂交（DISH）DNA探针混合检测法（检测基因及其所在17号染色体的着丝粒），对来自商业采购的原发性晚期或转移性UC的福尔马林固定、石蜡包埋组织进行检测。HER2临床状态分为HER2阴性（IHC 0）、HER2低表达（IHC 1+或IHC 2+/DISH未扩增）或HER2阳性（IHC 2+/DISH扩增或IHC 3+）。
在2024份UC样本中，HER2蛋白表达为IHC 0的有962份（47.5%），IHC 1+的有297份（14.7%），IHC 2+的有498份（24.6%），IHC 3+的有267份（13.2%）。原发性UC样本（52.2%，1028/1968）和转移性UC样本（60.7%，34/56；P = 0.26）中HER2表达肿瘤（IHC 1+、2+和3+）的百分比相似。基因在235例（11.6%）中扩增，其中分别有2.7%/3.7%/9.6%/56.2%的样本IHC评分为0/1+/2+/3+。总体而言，2024份UC组织样本中HER2临床状态为HER2阴性的有962份（47.5%；95%CI，45.4至49.7），HER2低表达的有747份（36.9%；95%CI，34.8至39.0），HER2阳性的有315份（15.6%；95%CI，14.0至17.2）。
我们观察到，使用标准化IHC方法检测，2024例晚期UC肿瘤中有超过50%表现出一定程度的HER2蛋白表达，而约12%的标本有基因扩增，包括约3%的IHC评分为0或1+的标本。有必要持续开发优化和标准化的HER2检测方法，以识别可能从新型HER2靶向治疗中获益的HER2表达型UC患者。
