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

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:

• urothelial carcinoma
• non-muscle-invasive
• c- KIT
• HER2

Abbreviations

AUC, area under the curve; BCG, Bacillus Calmette-Guérin; CIS, carcinoma in situ; HER2, human epidermal factor receptor 2; H&E, hematoxylin and eosin; IHC, immunohistochemistry; NMIBC, non-muscle-invasive bladder cancer; MIBC, muscle-invasive bladder cancer; TURBT, transurethral resection of bladder tumor.

Data Sharing Statement

The datasets supporting the conclusions of this article are included within the article and its supplementary file.

Ethics Approval and Consent to Participate

The study was approved by the local institutional ethical committee faculty of medicine, Suez Canal university with IRB no (4169), and informed consent was obtained from all patients who participated in the study. All the procedures done were in accordance with the Declaration of Helsinki.

Consent for Publication

Written informed consent was obtained from the patients for publication of this study and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.

Acknowledgments

The authors extend special thanks to M. Saad for his technical skills in preparing histopathological slides.

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

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.

Additional information

Funding

All clinicopathological studies in this study were funded by the authors.