Abstract

BackgroundThe role of epidermal growth factor (EGF) and its receptor (EGFR) in the pathogenesis and progression of various malignant tumors has long been known, but there is still disagreement concerning prognostic significance of EGFR expression in clear cell renal cell carcinoma (CCRCC). The present study was designed to analyze more objectively the protein EGFR expression in CCRCC and to compare its value with EGFR gene copy number changes and clinicopathologic characteristics including patient survival.MethodsThe protein EGFR expression was analyzed immunohistochemically on 94 CCRCC, and gene copy number alterations of EGFR by FISH analysis on 41 CCRCC selected according to distinct membrane EGFR staining.ResultsMembrane EGFR expression in tumor cells was heterogeneous with respect to the proportion of positive cells and staining intensity. FISH analysis did not reveal EGFR gene amplification, while polysomy of chromosome 7 found in 41% was associated with higher EGFR membrane expression. Moreover, EGFR overexpression was associated with a higher nuclear grade, larger tumor size and shorter patient's survival, while there was no connection with pathological stage.ConclusionIn conclusion, the protein expression of EGFR had an impact on prognosis in patients with CCRCC, while an increased copy number of chromosome 7 could be the possible reason for EGFR protein overexpression in the absence of gene amplification.

Highlights

  • The role of epidermal growth factor (EGF) and its receptor (EGFR) in the pathogenesis and progression of various malignant tumors has long been known, but there is still disagreement concerning prognostic significance of EGFR expression in clear cell renal cell carcinoma (CCRCC)

  • Prognostic significance of EGFR was confirmed in numerous studies [11,12,13], the association between EGFR expression and prognosis in clear cell renal cell carcinoma (CCRCC) is still controversial [14,15,16]

  • When the percentage of membrane EGFR expression was combined with the intensity of staining, the median value of tH-score and cH-score was 30 (0-257) and 15.6 (0-255), respectively

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Summary

Introduction

The role of epidermal growth factor (EGF) and its receptor (EGFR) in the pathogenesis and progression of various malignant tumors has long been known, but there is still disagreement concerning prognostic significance of EGFR expression in clear cell renal cell carcinoma (CCRCC). EGF and related growth factors such as TGF a, ampiregulin, betacellulin, neuregulins, epiregulin and heparin binding growth factor bind to the extracellular domain of EGFR resulting in receptor conformational change. This structural change allows for receptor dimerization and autophosphorylation of tyrosine kinase residues within the intracellular domain leading to activation of the signal transduction pathways. Pu at al suggests that different locations of EGFR expression may be associated with human renal tumorigenesis [14,15,16]

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