title: HER2 expression in locally advanced gastric cancer with extensive lymph node (bulky N2 or paraaortic) metastasis (JCOG1005-A trial).
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Upper Gastrointestinal Surgery, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Matsumoto
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Sasako
authors.forename: Junki
authors.initials: J
authors.lastname: Mizusawa
authors.forename: Seiichi
authors.initials: S
authors.lastname: Hirota
authors.forename: Atsushi
authors.initials: A
authors.lastname: Ochiai
authors.forename: Ryoji
authors.initials: R
authors.lastname: Kushima
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Katai
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Norimasa
authors.initials: N
authors.lastname: Fukushima
authors.forename: Atsushi
authors.initials: A
authors.lastname: Nashimoto
authors.forename: Akira
authors.initials: A
authors.lastname: Tsuburaya
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000401:mortality / Q000473:pathology / Q000601:surgery; D000328:Adult; D000368:Aged; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008198:Lymph Nodes / Q000473:pathology; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D015996:Survival Rate
chemical_list: D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human