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Aktuelle Urol. 2017 Aug;48(4):356-362. doi: 10.1055/s-0043-110403. Epub 2017 Jul 27.

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

[Article in German; Abstract available in German from the publisher]

Author information

1
Klinik für Urologie, Medizinische Fakultät Mannheim, Universität Heidelberg; Mannheim.
2
Klinik für Urologie und Kinderurologie, Universitätsklinikum Ulm; Ulm.
3
Stratifyer Molecular Pathology GmbH; Köln.
4
Institut für Pathologie, Medizinische Fakultät Mannheim, Universität Heidelberg, Mannheim.
5
Pathologie des Uni-Klinikums Erlangen, Nürnberg; Erlangen.

Abstract

in English, German

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.

PMID:
28750448
DOI:
10.1055/s-0043-110403
[Indexed for MEDLINE]

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