HER2 expression in locally advanced gastric cancer with extensive lymph node (bulky N2 or paraaortic) metastasis (JCOG1005-A trial)

Gastric Cancer. 2015 Jul;18(3):467-75. doi: 10.1007/s10120-014-0398-3. Epub 2014 Jul 4.


Background: Human epidermal growth factor receptor 2 (HER2) is likely overexpressed and/or amplified in locally advanced gastric cancer with extensive (bulky N2 or paraaortic) lymph node metastasis, and patients may benefit from treatment with anti-HER2 antibodies. This study evaluated the frequency of HER2 overexpression and amplification in The Japanese Gastric Cancer Association (JGCA)-N3 and JGCA-bulky N2 tumors and the correlation between HER2 status and survival.

Methods: HER2 status was assessed using immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) in tumor tissue samples from 89 patients with gastric adenocarcinoma enrolled in the phase II JCOG0001 and JCOG0405 trials. HER2 positivity was defined as IHC3+ or IHC2+ with confirmatory FISH results.

Results: Of the 89 tumor samples, 24 (27 %) showed HER2 positivity, including 16 scored as IHC3+ and 8 as IHC2+ and FISH positive. Multivariate analysis showed that the HER2 positivity rate was significantly higher in evaluable differentiated tumors than in undifferentiated tumors [18/44 (40.9 %) vs. 5/42 (11.9 %)]. Although the apparent OS curve of HER2 positive was superior to that of HER2 negative patients, HER2 status was not a statistically significant prognostic factor in multivariate analysis.

Conclusion: The HER2 positivity rate was relatively high in patients with JGCA-bulky N2 and JGCA-N3 gastric adenocarcinoma, suggesting that HER2 evaluation is essential to select the therapeutic regimen for neoadjuvant chemotherapy for this group of patients.

Publication types

  • Clinical Trial, Phase II
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / metabolism
  • Adenocarcinoma / mortality
  • Adenocarcinoma / pathology
  • Adenocarcinoma / surgery
  • Adult
  • Aged
  • Female
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization, Fluorescence
  • Lymph Nodes / pathology
  • Lymphatic Metastasis
  • Male
  • Middle Aged
  • Receptor, ErbB-2 / genetics
  • Receptor, ErbB-2 / metabolism*
  • Stomach Neoplasms / metabolism
  • Stomach Neoplasms / mortality
  • Stomach Neoplasms / pathology*
  • Stomach Neoplasms / surgery
  • Survival Rate


  • ERBB2 protein, human
  • Receptor, ErbB-2