HER2 status in gastric and gastroesophageal junction cancer assessed by local and central laboratories: Chinese results of the HER-EAGLE study

PLoS One. 2013 Nov 14;8(11):e80290. doi: 10.1371/journal.pone.0080290. eCollection 2013.

Abstract

Trastuzumab has been approved for human epidermal growth factor receptor 2 (HER2)-positive advanced gastric and gastroesophageal junction cancers (GC and GJC) in combination with chemotherapy. The aim of this HER2 early/advanced gastric epidemiology (HER-EAGLE) study was to evaluate the frequency of HER2 over-expression and to evaluate agreement on HER2 status assessment in GC and GJC patients in local laboratories versus a central laboratory in China. Tumor samples from 734 GC or GJC patients who were enrolled at 11 different hospitals in China were examined. HER2 status was assessed by immunohistochemistry (IHC), and followed by dual-color silver-enhanced in Situ hybridization (DSISH) in IHC 2+ cases. Clinicopathologic characteristics were collected from all of the patients. HER2-positive tumors were identified in 12.0% (88/734) of the GC and GJC cases. There were significantly higher rates of HER2 positivity in patients with GJC (GJC: 18.1%, GC: 9.7%, P=0.002), and intestinal-type cancers using the Lauren classification (intestinal: 23.6%, diffuse/mixed: 4.3%, P<0.0001). No significant difference in HER2 positivity was identified between resection and biopsy samples, or between early and advanced disease stages. The agreement between local laboratories and the central laboratory on HER2 status scoring was good (kappa=0.86). The main reason of HER2 status discordance between local and the central laboratories was IHC result mis-interpretation in local laboratories. These results suggest that IHC followed by DSISH testing is an accurate and cost-effective procedure in China.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / metabolism
  • Biomarkers, Tumor / pharmacology
  • Esophagogastric Junction / metabolism*
  • Esophagogastric Junction / pathology*
  • Female
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization
  • Male
  • Middle Aged
  • Receptor, ErbB-2 / genetics
  • Receptor, ErbB-2 / metabolism*
  • Stomach Neoplasms / metabolism
  • Stomach Neoplasms / pathology

Substances

  • Biomarkers, Tumor
  • ERBB2 protein, human
  • Receptor, ErbB-2

Grants and funding

This study was sponsored by Shanghai ROCHE pharmaceuticals Ltd. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials.