Evaluation of the Expression of HER2 and c-KIT Proteins as Prognostic Markers in Superficial Bladder Urothelial Carcinoma

BACKGROUND: The roles of c-KIT and HER2 protein expression in bladder cancer are still debated, and the prognostic value of these proteins as markers of tumor progression is inconclusive. OBJECTIVE: To assess the impact of HER2 and c-KIT protein expressions in the progression of non-muscle-invasive bladder cancer. METHODS: All patients undergoing transurethral resection of bladder tumors for non-muscle-invasive urothelial carcinoma, with standard regimen of BCG, between January 2017 and November 2019, were evaluated pathologically and immunohistochemically for HER1 and c-KIT proteins in urothelial carcinoma cells. Follow-up cystoscopy was performed for 100 patients every 3 months for the first 2-years and any recurred tumors were excised and examined pathologically, as well as stained for HER2 and c-KIT protein expression. RESULTS: HER2 and c-KIT positive expressions were detected in 49% and 38% of cases, respectively. After a mean follow-up of 26.4±7.2 months, the overall recurrence and progression rates were significantly correlated with overexpression of HER2 and c-KIT. In high-grade non-invasive muscle neoplasms, tumor cells showed weak expression for both HER2 and c-KIT proteins, but with progression to muscle-invasion, tumor cells strongly expressed HER2 and lost expression to c-KIT. In the multivariate model, overexpression of HER2 rather than c-KIT protein significantly predicted increased progression. CONCLUSION: Recurrence and progression of non-muscle-invasive bladder cancer correlate with overexpression of HER2 and c-KIT proteins in tumor cells.