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

Gastric Cancer, 2015, Vol.18(3), pp.467-475 [Peer Reviewed Journal]

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  • Title:
    HER2 expression in locally advanced gastric cancer with extensive lymph node (bulky N2 or paraaortic) metastasis (JCOG1005-A trial)
  • Author: Matsumoto, Tomohiro ; Sasako, Mitsuru ; Mizusawa, Junki ; Hirota, Seiichi ; Ochiai, Atsushi ; Kushima, Ryoji ; Katai, Hitoshi ; Tanaka, Yoichi ; Fukushima, Norimasa ; Nashimoto, Atsushi ; Tsuburaya, Akira
  • Found In: Gastric Cancer, 2015, Vol.18(3), pp.467-475 [Peer Reviewed Journal]
  • Subjects: Gastric adenocarcinoma ; HER2 status ; Immunohistochemistry ; Trastuzumab
  • Language: English
  • Description: Byline: Tomohiro Matsumoto (1), Mitsuru Sasako (1), Junki Mizusawa (2), Seiichi Hirota (3), Atsushi Ochiai (4), Ryoji Kushima (5), Hitoshi Katai (6), Yoichi Tanaka (7), Norimasa Fukushima (8), Atsushi Nashimoto (9), Akira Tsuburaya (10) Keywords: Gastric adenocarcinoma; HER2 status; Immunohistochemistry; Trastuzumab 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. 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. Author Affiliation: (1) Department of Upper Gastrointestinal Surgery, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, Japan (2) Japan Clinical Oncology Group Data Center, Multi-Center Clinical Trial Support Center, National Cancer Center, Tokyo, Japan (3) Department of Surgical Pathology, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan (4) Pathology Division, Research Center for Innovative Oncology, National Cancer Center Hospital East, Kashiwa, Chiba, Japan (5) Pathology and Clinical Laboratory Division, National Cancer Center Hospital, Tokyo, Japan (6) Gastric Surgery Division, National Cancer Center Hospital, Tokyo, Japan (7) Division of Gastroenterological Surgery, Saitama Cancer Center, Saitama, Japan (8) Department of Surgery, Yamagata Prefectural Central Hospital, Yamagata, Japan (9) Department of Surgery, Niigata Cancer Center Hospital, Niigata, Japan (10) Department of Gastrointestinal Surgery, Kanagawa Cancer Center, Yokohama, Japan Article History: Registration Date: 18/06/2014 Received Date: 01/02/2014 Accepted Date: 11/06/2014 Online Date: 04/07/2014
  • Identifier: ISSN: 1436-3291 ; E-ISSN: 1436-3305 ; DOI: 10.1007/s10120-014-0398-3

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