Demonstration of EGFR gene copy loss in colorectal carcinomas by fluorescence in situ hybridization (FISH): a surrogate marker for sensitivity to specific anti-EGFR therapy?

Histopathology. 2005 Dec;47(6):560-4. doi: 10.1111/j.1365-2559.2005.02252.x.

Abstract

Aims: To investigate EGFR gene copy number heterogeneity in colorectal carcinomas compared with copy number of chromosome 7 and immunohistochemical expression of the EGFR protein.

Methods and results: Fluorescence in situ hybridization of the EGFR gene and CEP7 was carried out on paraffin-embedded material from 48 rectal carcinomas combined with immunohistochemical detection of EGFR with a polymer detection kit. EGFR gene copy number had a range of 1.4-7.3 with a mean of 2.5. CEP7 copy number had a range of 1.5-6.1 with a mean of 2.5. The EGFR gene/CEP7 ratio ranged from 0.4 to 1.5 with a mean of 0.96. Most cases had a balanced EGFR gene/CEP7 ratio (37 cases = 77%). Copy gain was found in seven cases (15%) with a ratio of up to 1.5, consistent with gain of one EGFR gene copy in one chromosome. Copy loss was found in four cases (8%). All cases with EGFR gene copy loss were immunohistochemically positive.

Conclusions: Demonstration of EGFR gene copy loss might be a surrogate marker for EGFR mutation/deletion and could be used in a routine setting in pathology departments. Further studies are needed to determine whether this may be used to select patients that might benefit from specific anti-EGFR therapy.

Publication types

  • Comparative Study

MeSH terms

  • Biomarkers, Tumor
  • Carcinoma / genetics*
  • Carcinoma / metabolism
  • Carcinoma / pathology
  • Chromosomes, Human, Pair 7
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / metabolism
  • Colorectal Neoplasms / pathology
  • Colorectal Neoplasms / therapy
  • ErbB Receptors / genetics*
  • ErbB Receptors / metabolism
  • Gene Dosage*
  • Gene Expression
  • Genes, erbB-1*
  • Genes, erbB-2
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization, Fluorescence*
  • Sensitivity and Specificity

Substances

  • Biomarkers, Tumor
  • ErbB Receptors