Significance of estrogen receptor 1 (ESR-1) gene imbalances in colon and hepatocellular carcinomas based on tissue microarrays analysis

Med Oncol. 2011 Dec;28(4):934-40. doi: 10.1007/s12032-010-9554-8. Epub 2010 May 11.


Estrogen receptor alpha-encoded by ESR1 gene-overexpression correlates with prognosis and response to specific chemotherapy in breast adenocarcinoma cases. Mechanisms of ESR-1 deregulation in carcinomas remain under investigation. To analyze ESR1 in carcinomas of different histogenesis. Using tissue microarray technology, 172 primary carcinomas including breast ductal adenocarcinomas (n=60), hepatocellular carcinomas (n=52), and colon adenocarcinomas (n=60) were cored and re-embedded in three paraffin blocks. Initial diagnosis was based on liquid based cytology (LiquiPrep/ThinPrep). Immunohistochemistry and fluorescence in situ hybridization were performed. Quantitative evaluation of ER-a protein levels was assessed by applying digital image analysis. ER-a overexpression was observed in 41/60 (68.3%), 23/52 (44.2%) and 4/60 (6.6%) cases, respectively. ESR1 gene multiple copies were confirmed in 13/60 (21.6%) breast adenocarcinomas, but high amplification only in 8/13 (62.8%). Allelic absence was identified in 3/52 (5.7%) hepatocellular carcinomas, whereas colon adenocarcinomas demonstrated gene gains in 5/60 (8.3%) cases referred to chr 6 aneuploidy and not to amplification. ER-a overall expression was associated strongly to ESR1 gene copies only in breast carcinoma (P=0.036). ESR-1 gene overexpression happens frequently in breast cancer, but only a subset of them are high amplified cases correlated to increased response rates in hormonal therapy (tamoxifen). Absence of this mechanism in hepatocellular and colon carcinomas maybe is a negative factor for applying this therapy. This is a pattern of histo-genetic depended targeted therapeutic strategy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / genetics*
  • Breast Neoplasms / genetics
  • Breast Neoplasms / pathology
  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / pathology
  • Colonic Neoplasms / genetics*
  • Colonic Neoplasms / pathology
  • Estrogen Receptor alpha / genetics*
  • Female
  • Gene Amplification
  • Gene Expression Profiling
  • Humans
  • Image Interpretation, Computer-Assisted
  • Immunohistochemistry
  • In Situ Hybridization, Fluorescence
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / pathology
  • Neoplasm Grading
  • Neoplasm Staging
  • Tissue Array Analysis


  • ESR1 protein, human
  • Estrogen Receptor alpha