Summary: | Wael Abdou Hassan, 1 Essam Shalaby, 2 Mona Abo Hashesh, 3 Rehab Ibrahim Ali 4, 5 1Department of Basic Sciences, College of Medicine, Suliman Al Rajhi University, Al Bukayriyah, Kingdom of Saudi Arabia; 2Department of Urology, Faculty of Medicine, Suez Canal University, Ismailia, Egypt; 3Faculty of Science, Port Said University, Port Said, Egypt; 4Department of Pathology, College of Medicine, El-Jouf University, Sakaka, Kingdom of Saudi Arabia; 5Department of Pathology, Faculty of Medicine, Suez Canal University, Ismailia, EgyptCorrespondence: Wael Abdou HassanDepartment of Basic Sciences, College of Medicine, Suliman Al Rajhi University, PO Box 777, Al Bukayriyah, 51941, Kingdom of Saudi ArabiaTel +966-16 316 9000Email w.hassan@sr.edu.saBackground: 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.Keywords: urothelial carcinoma, non-muscle-invasive, c- KIT, HER2
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