PMID- 22161775 OWN - NLM STAT- MEDLINE DCOM- 20120430 LR - 20181201 IS - 1097-0142 (Electronic) IS - 0008-543X (Linking) VI - 118 IP - 5 DP - 2012 Mar 1 TI - Epidermal growth factor receptor protein expression and genomic alterations in renal cell carcinoma. PG - 1268-75 LID - 10.1002/cncr.26436 [doi] AB - 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. FAU - Minner, Sarah AU - Minner S AD - Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. s.minner@uke.uni-hamburg.de FAU - Rump, Dorothea AU - Rump D FAU - Tennstedt, Pierre AU - Tennstedt P FAU - Simon, Ronald AU - Simon R FAU - Burandt, Eike AU - Burandt E FAU - Terracciano, Luigi AU - Terracciano L FAU - Moch, Holger AU - Moch H FAU - Wilczak, Waldemar AU - Wilczak W FAU - Bokemeyer, Carsten AU - Bokemeyer C FAU - Fisch, Margit AU - Fisch M FAU - Sauter, Guido AU - Sauter G FAU - Eichelberg, Christian AU - Eichelberg C LA - eng PT - Journal Article PL - United States TA - Cancer JT - Cancer JID - 0374236 RN - EC 2.7.10.1 (EGFR protein, human) RN - EC 2.7.10.1 (ErbB Receptors) SB - IM MH - Carcinoma, Renal Cell/epidemiology/*genetics/*metabolism/pathology MH - Chromosome Aberrations/statistics & numerical data MH - DNA Mutational Analysis MH - ErbB Receptors/*genetics/*metabolism MH - Gene Dosage MH - Gene Expression Regulation, Neoplastic MH - Genome, Human MH - Humans MH - Immunohistochemistry MH - In Situ Hybridization, Fluorescence MH - Kidney Neoplasms/epidemiology/*genetics/*metabolism/pathology MH - Mutation/physiology MH - Neoplasm Staging MH - Tissue Array Analysis EDAT- 2011/12/14 06:00 MHDA- 2012/05/01 06:00 CRDT- 2011/12/14 06:00 PHST- 2011/12/14 06:00 [entrez] PHST- 2011/12/14 06:00 [pubmed] PHST- 2012/05/01 06:00 [medline] AID - 10.1002/cncr.26436 [doi] PST - ppublish SO - Cancer. 2012 Mar 1;118(5):1268-75. doi: 10.1002/cncr.26436.