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 three-tier assessment can effectively predict clinical prognosis of urothelial carcinoma.