Clinical testing experience and relationship to EGFR gene copy number and immunohistochemical expression Journal Article


Authors: Li, A. R.; Chitale, D.; Riely, G. J.; Pao, W.; Miller, V. A.; Zakowski, M. F.; Rusch, V.; Kris, M. G.; Ladanyi, M.
Article Title: Clinical testing experience and relationship to EGFR gene copy number and immunohistochemical expression
Abstract: Lung adenocarcinomas responsive to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors possess EGFR mutations and often increased EGFR copy number. We prospectively studied 334 clinical cases using polymerase chain reaction-based assays to detect deletions within exon 19 and the L858R mutation in exon 21, which together account for approximately 90% of EGFR mutations. Seventy-eight (23%) of these tumors had an EGFR mutation, with 55 (71%) exon 19 deletions and 23 (29%) exon 21 L858R mutations. We were able to compare mutant and normal EGFR alleles and found a preferential amplification of the mutant allele. The association of mutations with EGFR amplification (determined by chromogenic in situ hybridization) and EGFR expression (determined by immunohistochemistry) was further examined in a subset of 60 tumors. EGFR amplification (≥5 EGFR signals per nucleus) was seen in 15 of 29 (52%) EGFR-mutated tumors but in only five of 31 (6%) non-mutated tumors (P = 0.006). EGFR overexpression was strongly associated with amplification but was statistically independent of EGFR mutation. Most patients with EGFR mutations (17 of 29, 59%) never smoked compared with 13% (four of 31) of patients lacking such mutations (P = 0.0003). The association of amplification with smoking status was marginal and was non-existent with EGFR expression. Thus, these results indicate that EGFR amplification, preferentially of the mutant allele, often accompanies EGFR mutation, whereas EGFR immunohistochemical staining associates with amplification but cannot predict EGFR mutation status. Copyright © American Society for Investigative Pathology and the Association for Molecular Pathology.
Keywords: immunohistochemistry; adult; controlled study; human tissue; protein expression; aged; gene mutation; exon; gene deletion; genetics; mutation; prospective study; polymerase chain reaction; adenocarcinoma; metabolism; allele; gene overexpression; proto oncogene; gene amplification; lung neoplasms; epidermal growth factor receptor; genetic association; smoking; receptor, epidermal growth factor; pathology; lung tumor; in situ hybridization; lung adenocarcinoma; nucleotide sequence; tissue array analysis; dna mutational analysis; tissue microarray; genes, erbb-1
Journal Title: Journal of Molecular Diagnostics
Volume: 10
Issue: 3
ISSN: 1525-1578
Publisher: Elsevier Science, Inc.  
Date Published: 2008-05-01
Start Page: 242
End Page: 248
Language: English
DOI: 10.2353/jmoldx.2008.070178
PUBMED: 18403609
PROVIDER: scopus
PMCID: PMC2329789
DOI/URL:
Notes: --- - "Cited By (since 1996): 40" - "Export Date: 17 November 2011" - "CODEN: JMDIF" - "Source: Scopus"
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MSK Authors
  1. Allan Rongguo Li
    24 Li
  2. Valerie W Rusch
    869 Rusch
  3. William Pao
    141 Pao
  4. Dhananjay Arun Chitale
    33 Chitale
  5. Vincent Miller
    270 Miller
  6. Marc Ladanyi
    1333 Ladanyi
  7. Gregory J Riely
    605 Riely
  8. Maureen F Zakowski
    289 Zakowski
  9. Mark Kris
    872 Kris