title: Epidermal growth factor receptor protein expression and genomic alterations in renal cell carcinoma.
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.
authors.affiliation: Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. s.minner@uke.uni-hamburg.de
authors.forename: Sarah
authors.initials: S
authors.lastname: Minner
authors.forename: Dorothea
authors.initials: D
authors.lastname: Rump
authors.forename: Pierre
authors.initials: P
authors.lastname: Tennstedt
authors.forename: Ronald
authors.initials: R
authors.lastname: Simon
authors.forename: Eike
authors.initials: E
authors.lastname: Burandt
authors.forename: Luigi
authors.initials: L
authors.lastname: Terracciano
authors.forename: Holger
authors.initials: H
authors.lastname: Moch
authors.forename: Waldemar
authors.initials: W
authors.lastname: Wilczak
authors.forename: Carsten
authors.initials: C
authors.lastname: Bokemeyer
authors.forename: Margit
authors.initials: M
authors.lastname: Fisch
authors.forename: Guido
authors.initials: G
authors.lastname: Sauter
authors.forename: Christian
authors.initials: C
authors.lastname: Eichelberg
mesh_terms: D002292:Carcinoma, Renal Cell / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D002869:Chromosome Aberrations / Q000706:statistics & numerical data; D004252:DNA Mutational Analysis; D066246:ErbB Receptors / Q000235:genetics* / Q000378:metabolism*; D018628:Gene Dosage; D015972:Gene Expression Regulation, Neoplastic; D015894:Genome, Human; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D007680:Kidney Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D009154:Mutation / Q000502:physiology; D009367:Neoplasm Staging; D046888:Tissue Array Analysis
chemical_list: C512478:EGFR protein, human; D066246:ErbB Receptors