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. 2021 May 5:13:197-206.
doi: 10.2147/RRU.S296974. eCollection 2021.

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

Wael Abdou Hassan  1 , Essam Shalaby  2 , Mona Abo-Hashesh  3 , Rehab Ibrahim Ali  4   5
Affiliations

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

Wael Abdou Hassan et al. Res Rep Urol. .

Abstract

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.

Keywords: HER2; c- KIT; non-muscle-invasive; urothelial carcinoma.

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Conflict of interest statement

None of the contributing authors have any conflict of interest, including specific financial interests or relationships and affiliations relevant to the subject matter or materials discussed in the manuscript.

Figures

Figure 1
Figure 1
Expression of HER2 and c-KIT in progressive urothelial lesions. Representative immunohistochemical (IHC) expression for HER2 and c-KIT markers. The immunoreaction (brown) for HER2 and c-KIT was detected in the cytosol and cell membranes. (A) In low-grade NMIBC, tumor nests (black arrows) showed expression of HER2 as 2+, while that of c-KIT was weak and focal (1+) (IHC original magnification x200). In low-grade muscle-invasive BC, tumor nests (black arrows) are seen dissecting muscle bundles (black arrows). The expression of HER2 was reduced in comparison to NMIBC but detected in 50% of tumor cells and thus scored 1+, while there was no expression for c-KIT. (IHC original magnification x200, scale bar 50 µm). NMIBC; non-muscle-invasive bladder carcinoma. (B) In high-grade NMIBC, tumor nests (black arrows) composed of malignant urothelial cells show weak and focal expression of both HER2 and c-KIT (1+) (IHC original magnification x200). In high-grade muscle-invasive BC, tumor nests are seen dissecting muscle bundles (black arrows). The expression of HER2 significantly increased in comparison to NMIBC (scored 2+), while there was no expression for c-KIT. (H&E and IHC original magnification x200, scale bar 50 µm).
Figure 2
Figure 2
Receiver operating characteristic (ROC) curves for the impact of HER2 and c-KIT expression on recurrence (A) and progression (B).
See this image and copyright information in PMC

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