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Epidermal growth factor receptor protein expression and genomic alterations in renal cell carcinoma


Minner, S; Rump, D; Tennstedt, P; Simon, R; Burandt, E; Terracciano, L; Moch, H; Wilczak, W; Bokemeyer, C; Fisch, M; Sauter, G; Eichelberg, C (2012). Epidermal growth factor receptor protein expression and genomic alterations in renal cell carcinoma. Cancer, 118(5):1268-1275.

Abstract

BACKGROUND:

Epidermal growth factor receptor (EGFR) is involved in the progression of many cancer types and represents an important therapeutic target.
METHODS:

To determine the role of EGFR in renal cell carcinoma (RCC), the authors analyzed 1088 tumors in a tissue microarray format by using immunohistochemistry and fluorescence in situ hybridization (FISH). A subset of 63 cancers was sequenced for EGFR exon 18 through 21 mutations.
RESULTS:

EGFR expression was observed in 83.8% of clear cell carcinomas, in 68.2% of papillary carcinomas, in 75% of chromophobe carcinomas, and in 50% of oncocytomas. Within clear cell carcinomas, the expression level of EGFR was associated with high tumor grade (P < .0001), advanced pathologic tumor classification (P < .0001), and, to a lesser extent, lymph node status (P = .0326). FISH analysis revealed increased EGFR copy numbers (high polysomy) in 5.5% of tumors and amplification in 0.1% of tumors. EGFR copy number increases were associated with EGFR protein expression (P = .0015). Within clear cell carcinomas, EGFR copy number increases were associated with high tumor grade (P < .0001), advanced pathologic tumor classification (P = .0472), and lymph node status (P = .0065). No exon 18 through 21 mutations were identified in 63 sequenced tumors.
CONCLUSIONS:

The authors concluded that increased EGFR expression occurs in a fraction of patients who have RCC with an unfavorable histologic phenotype. EGFR copy number gain represents 1 possible cause for EGFR overexpression; however, many over expressing tumors have a normal genotype. High polysomy (which is suggested to be predictive of a response to tyrosine kinase inhibitors) occurs in 5.6% of RCCs. Thus, the potential utility of anti-EGFR medications may be worth further investigation in a small but significant subset of patients with RCC. Cancer 2011;. © 2011 American Cancer Society.

Copyright © 2011 American Cancer Society.

Abstract

BACKGROUND:

Epidermal growth factor receptor (EGFR) is involved in the progression of many cancer types and represents an important therapeutic target.
METHODS:

To determine the role of EGFR in renal cell carcinoma (RCC), the authors analyzed 1088 tumors in a tissue microarray format by using immunohistochemistry and fluorescence in situ hybridization (FISH). A subset of 63 cancers was sequenced for EGFR exon 18 through 21 mutations.
RESULTS:

EGFR expression was observed in 83.8% of clear cell carcinomas, in 68.2% of papillary carcinomas, in 75% of chromophobe carcinomas, and in 50% of oncocytomas. Within clear cell carcinomas, the expression level of EGFR was associated with high tumor grade (P < .0001), advanced pathologic tumor classification (P < .0001), and, to a lesser extent, lymph node status (P = .0326). FISH analysis revealed increased EGFR copy numbers (high polysomy) in 5.5% of tumors and amplification in 0.1% of tumors. EGFR copy number increases were associated with EGFR protein expression (P = .0015). Within clear cell carcinomas, EGFR copy number increases were associated with high tumor grade (P < .0001), advanced pathologic tumor classification (P = .0472), and lymph node status (P = .0065). No exon 18 through 21 mutations were identified in 63 sequenced tumors.
CONCLUSIONS:

The authors concluded that increased EGFR expression occurs in a fraction of patients who have RCC with an unfavorable histologic phenotype. EGFR copy number gain represents 1 possible cause for EGFR overexpression; however, many over expressing tumors have a normal genotype. High polysomy (which is suggested to be predictive of a response to tyrosine kinase inhibitors) occurs in 5.6% of RCCs. Thus, the potential utility of anti-EGFR medications may be worth further investigation in a small but significant subset of patients with RCC. Cancer 2011;. © 2011 American Cancer Society.

Copyright © 2011 American Cancer Society.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Institute of Pathology and Molecular Pathology
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:2012
Deposited On:21 Jan 2012 16:20
Last Modified:05 Apr 2016 15:25
Publisher:Wiley-Blackwell
ISSN:0008-543X
Publisher DOI:https://doi.org/10.1002/cncr.26436
PubMed ID:22161775

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