Distinct clinical features of urothelial carcinoma with low-expressing human epidermal growth factor receptor 2 status

Background: Some urothelial carcinoma patients are ineligible for platinum-based chemotherapy, necessitating exploration of other effective therapeutic strategies. Human epidermal growth factor receptor 2 (HER2) protein overexpression, gene amplification or mutations exist in urothelial carcinoma. Our study is to investigate the correlation of three-tier assessment of HER2 expression with clinical pathological characteristics and prognosis of urothelial carcinoma. Methods: HER2 expression in 75 urothelial carcinomas from Jiangsu Cancer Hospital was re-scored by immunohistochemistry and fluorescence in situ hybridization according to HER2 three-tier assessment standards. Its relationship with various pathological parameters of urothelial carcinoma and its correlation with prognosis were analyzed. And validate in The Cancer Genome Atlas (TCGA) cohort. Results: HER2 expression was observed in 82.7% (62/75) of urothelial carcinoma patients, of which HER2-low expression accounted for 61.3% (46/75). HER2 expression was significantly correlated with the tumor-nodes-metastasis (TNM) stage of urothelial carcinoma (P=0.043) and HER2-low was an independent poor prognostic factor for patients with urothelial carcinoma (P=0.04). Follow-up showed that HER2-low patients had the worst prognosis compared with HER2-negative (P=0.02) and HER2 positive (P=0.02) and also had the highest progression rate in TCGA cohort (P=0.02); receiver operator characteristic (ROC) model suggested HER2-low could effectively predict prognosis. Conclusions: HER2 expression is closely related to the TNM stage of urothelial carcinoma; HER2 threetier assessment can effectively predict clinical prognosis of urothelial carcinoma.