Expression and amplification of Her2, EGFR and cyclin D1 in breast cancer: immunohistochemistry and chromogenic in situ hybridization

Pathol Int. 2008 Jan;58(1):17-25. doi: 10.1111/j.1440-1827.2007.02183.x.

Abstract

Determination of Her2, epidermal growth factor receptor (EGFR) and cyclin D1 status is now of major clinical importance due to the development of molecule-targeting drugs in anticancer therapy. Immunohistochemistry (IHC) and chromogenic in situ hybridization (CISH) are the most simple and convenient methods for evaluating gene alterations and their protein consequences. The purpose of the present study was to investigate the status of Her2, EGFR and cyclin D1 on both IHC and CISH in 95 primary breast carcinomas. There was substantial consistency between the IHC and CISH results of Her2 and EGFR, showing fair agreement between protein overexpression and gene amplification. However, cyclin D amplification was not related to protein overexpression. Moreover, there was no correlation between Her2, EGFR and cyclin D1. Her2 protein overexpression and amplification were positively associated with histological grade, nuclear grade and inversely correlated with the expression of estrogen receptor (ER) and progesterone receptor (PR). In ER-negative and postmenopausal patients, EGFR gene amplification was strongly associated with worse recurrence-free survival (P = 0.0087, P = 0.0149, respectively). Overall, the present findings suggest that EGFR gene amplification is important in predicting prognosis and this should be evaluated in breast carcinoma in addition to Her2 status in routine pathological practice.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor / analysis
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / metabolism*
  • Chromogenic Compounds
  • Cyclin D1 / biosynthesis
  • Cyclin D1 / genetics
  • ErbB Receptors / biosynthesis
  • ErbB Receptors / genetics
  • Female
  • Gene Amplification
  • Gene Expression
  • Gene Expression Profiling* / methods
  • Genes, bcl-1 / physiology*
  • Genes, erbB-1 / physiology*
  • Genes, erbB-2 / physiology*
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization
  • Middle Aged
  • Receptor, ErbB-2 / biosynthesis
  • Receptor, ErbB-2 / genetics

Substances

  • Biomarkers, Tumor
  • Chromogenic Compounds
  • Cyclin D1
  • ErbB Receptors
  • Receptor, ErbB-2