Role of the human ErbB family receptors in urothelial carcinoma of the bladder: mRNA expression status and prognostic relevance

Erben P, Wezel F, Wirtz R, Martini T, Stein D, Weis CA, Hartmann A, Bolenz C (2017)

Publication Type: Journal article

Publication year: 2017

Journal

Aktuelle Urologie Georg Thieme Verlag

Book Volume: 48

Pages Range: 356-362

Journal Issue: 4

DOI: 10.1055/s-0043-110403

Abstract

Background Altered expression of epidermal growth factor (EGF) family (ErbB) receptors in urothelial carcinoma of the urinary bladder (UCB) has been associated with adverse outcomes. Given the limited treatment options in UCB, EGFR and HER2 (ERBB2) represent established therapeutic targets in other entities. We assessed the expression of ErbB family receptors (ERBB1 - 4) on mRNA levels in correlation with histopathological and clinical parameters in patients treated with radical cystectomy (RC). Methods 94 patients (female = 22; male = 72; median age: 66.5 years [range 39 - 88]) with UCB (pT1 - 4) treated with RC were included. Median follow-up was 28.2 months (range 0.6 - 139). ErbB mRNA expression levels were determined after extraction from formalin-fixed, paraffin-embedded tissue. Univariate and multivariate Cox proportional hazard models were performed to assess recurrence-free survival (RFS) and cancer-specific survival (CSS). Results Overexpression was observed in 18 % (ERBB3), 39 % (EGFR), 34 % (HER2, ERBB2) and 30 % (ERBB4) of patients, respectively. Higher pathological stage (p = 0.012), a positive nodal status (p = 0.0002), high ERBB4 (p = 0.012) and high HER2 (ERBB2) levels (p = 0.014) were significantly associated with reduced RFS. A negative lymph node status (p = 0.0003) and low HER2 (ERBB2) (p = 0.042) levels had a favourable prognostic impact on CSS. In multivariate analysis, positive pN stage (p = 0.0011) and high ERBB4 (p = 0.0073) expression were independent predictors of reduced RFS. Higher pN stage (p = 0.0016) was an independent predictor of reduced CSS. Conclusions Higher HER2 (ERBB2) expression is associated with an unfavourable prognosis in patients with UCB. However, it is not an independent predictor when measured on mRNA levels. Further analyses need to clarify which patients may still benefit from HER2 (ERBB2) targeted drugs.

Authors with CRIS profile

Arndt Hartmann Lehrstuhl für Allgemeine Pathologie und Pathologische Anatomie

Involved external institutions

Ruprecht-Karls-Universität Heidelberg DE Germany (DE) Universitätsklinikum Ulm DE Germany (DE) STRATIFYER Molecular Pathology GmbH DE Germany (DE)

How to cite

APA:

Erben, P., Wezel, F., Wirtz, R., Martini, T., Stein, D., Weis, C.-A.,... Bolenz, C. (2017). Role of the human ErbB family receptors in urothelial carcinoma of the bladder: mRNA expression status and prognostic relevance. Aktuelle Urologie, 48(4), 356-362. https://doi.org/10.1055/s-0043-110403

MLA:

Erben, Philipp, et al. "Role of the human ErbB family receptors in urothelial carcinoma of the bladder: mRNA expression status and prognostic relevance." Aktuelle Urologie 48.4 (2017): 356-362.

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