HER2 Genetic Heterogeneity in Gastric Cancer: Evaluation According to the College of American Pathologists Breast Cancer Criteria

Appl Immunohistochem Mol Morphol. 2015 Oct;23(9):628-32. doi: 10.1097/PAI.0000000000000136.

Abstract

Gastric and gastroesophageal junction (GEJ) adenocarcinomas have been shown to display significant HER2 genetic heterogeneity (GH). This is typically seen as a cluster of HER2-positive cells but can also take the form of intermingled cells, referred to a "mosaic" pattern. GH is not well defined in gastric/GEJ tumors and the "mosaic" pattern has never been studied. We sought to evaluate the frequency and distribution of the "mosaic" pattern of GH in gastric/GEJ tumors using the College of American Pathologists-endorsed breast criteria of 5% to <50% amplified nuclei. We also postulated that the lower limit of this GH definition might be seen by chance in normal gastric epithelium. A total of 360 consecutive gastric/GEJ tumors were tested for HER2 by immunohistochemistry and in situ hybridization. Individual tumor cell HER2:CEP17 ratios were calculated for each case and the percentage of tumor cells with a ratio ≥2.0 determined. In addition, 300 normal gastric epithelial cells were scored for HER2 and CEP17 signals. Overall, 265 cases (73.4%) showed GH. The percentage of amplified cells in GH cases linearly correlated with the overall HER2:CEP17 ratio. In normal gastric epithelium, a cell with an "amplified" 2:1 ratio was seen in 9.7% (29/300) of cells, thus reaching GH. The chance of "GH" in scoring 20 normal epithelial cells was 87%. We conclude that GH is very common in gastric/GEJ tumors when College of American Pathologists breast criteria are applied and the lower threshold is likely of little clinical significance due to the finding "amplified" 2:1 nuclei in normal cells.

MeSH terms

  • Adenocarcinoma / diagnosis
  • Adenocarcinoma / genetics*
  • Adenocarcinoma / metabolism
  • Adenocarcinoma / pathology
  • Adult
  • Aged
  • Aged, 80 and over
  • Centromere / genetics
  • Centromere / pathology
  • Chromosomes, Human, Pair 17 / genetics
  • Epithelial Cells / metabolism
  • Epithelial Cells / pathology
  • Esophageal Neoplasms / diagnosis
  • Esophageal Neoplasms / genetics*
  • Esophageal Neoplasms / metabolism
  • Esophageal Neoplasms / pathology
  • Esophagogastric Junction / metabolism
  • Esophagogastric Junction / pathology
  • Female
  • Gene Expression
  • Genetic Heterogeneity*
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization, Fluorescence
  • Male
  • Middle Aged
  • Mosaicism
  • Practice Guidelines as Topic
  • Receptor, ErbB-2 / genetics*
  • Receptor, ErbB-2 / metabolism
  • Retrospective Studies
  • Stomach Neoplasms / diagnosis
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / metabolism
  • Stomach Neoplasms / pathology
  • Trisomy / genetics*
  • Trisomy / pathology

Substances

  • ERBB2 protein, human
  • Receptor, ErbB-2

Supplementary concepts

  • Chromosome 17 trisomy