HER2 amplification and overexpression are significantly correlated in mucinous epithelial ovarian cancer

Hum Pathol. 2014 Apr;45(4):810-6. doi: 10.1016/j.humpath.2013.11.016. Epub 2013 Dec 12.

Abstract

HER2 gene amplification and protein over-expression are important factors in predicting clinical sensitivity to anti-HER2 therapies in breast, gastric or gastroesophageal junction cancer patients. The aim of this study was to evaluate the correlation between HER2 gene copy numbers and HER2 protein expressions in mucinous epithelial ovarian cancer (EOC). Of the 49 tissue microarray samples of mucinous EOC, we applied 2010 ToGA trial (Trastuzumab for Gastric Cancer) surgical specimen scoring criteria to analyze the HER2 protein expression by an immunohistochemistry (IHC) test with Dako (Carpenteria, CA), c-erb-B2 antibody, and the HER2 gene amplification by the fluorescence in situ hybridization (FISH) test with Abbott/Vysis PathVysion HER2 DNA Probe Kit (Abbott Molecular Inc., Des Plaines, IA). We achieved a high overall concordance of 97.56% between nonequivocal HER2 results by IHC and FISH tests. In addition, HER2 gene copies before chromosome-17 correction increased significantly in a stepwise order through the negative, equivocal and positive IHC result categories (P<.001), as did the HER2 gene copies after chromosome-17 correction (P<.001). On the other hand, HER2 IHC results correlated significantly with both chromosome-17-uncorrected HER2 gene copy numbers (ρ=0.630, P<.001) and chromosome-17 corrected HER2 gene copy numbers (ρ=0.558, P<.001). We concluded that both chromosome-17 corrected and uncorrected HER2 gene copies correlated significantly with HER2 IHC results. Tests for the HER2 gene copies per tumor cell either before or after correction of chromosome-17 can be applied as a potentially valuable tool to analyze the HER2 status in mucinous EOC.

Keywords: HER2; Mucinous epithelial ovarian cancer; Polysomy-17.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma, Mucinous / genetics*
  • Adenocarcinoma, Mucinous / metabolism
  • Chromosomes, Human, Pair 17 / genetics
  • Female
  • Gene Amplification*
  • Gene Dosage
  • Gene Expression Profiling / methods*
  • Genes, erbB-2 / genetics*
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization, Fluorescence
  • Ovarian Neoplasms / genetics*
  • Ovarian Neoplasms / metabolism
  • Receptor, ErbB-2 / biosynthesis*
  • Receptor, ErbB-2 / genetics
  • Tissue Array Analysis

Substances

  • ERBB2 protein, human
  • Receptor, ErbB-2