[Role of the human ErbB family receptors in urothelial carcinoma of the bladder: mRNA expression status and prognostic relevance] | Health & Environmental Research Online (HERO)

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Citation
Tags

HERO ID

4460837

Reference Type

Journal Article

Title

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

Author(s)

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

Year

2017

Is Peer Reviewed?

Yes

Journal

Aktuelle Urologie
ISSN: 0001-7868

Volume

Issue

Page Numbers

356-362

Language

German

PMID

28750448

DOI

10.1055/s-0043-110403

Web of Science Id

WOS:000406491900017

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.

Keywords

bladder cancer; urothelial carcinoma; radical cystectomy; HER2; ERBB2; prognostic factors