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

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...

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Published in:Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association 2015-07, Vol.18 (3), p.467-475
Main Authors: Matsumoto, Tomohiro, Sasako, Mitsuru, Mizusawa, Junki, Hirota, Seiichi, Ochiai, Atsushi, Kushima, Ryoji, Katai, Hitoshi, Tanaka, Yoichi, Fukushima, Norimasa, Nashimoto, Atsushi, Tsuburaya, Akira
Format: Article
Language:English
Subjects:
Abdominal Surgery
Adenocarcinoma - metabolism
Adenocarcinoma - mortality
Adenocarcinoma - pathology
Adenocarcinoma - surgery
Adult
Aged
Cancer Research
Female
Gastric cancer
Gastroenterology
Humans
Immunohistochemistry
In Situ Hybridization, Fluorescence
Lymph Nodes - pathology
Lymphatic Metastasis
Male
Medicine
Medicine & Public Health
Middle Aged
Oncology
Original Article
Receptor, ErbB-2 - genetics
Receptor, ErbB-2 - metabolism
Stomach Neoplasms - metabolism
Stomach Neoplasms - mortality
Stomach Neoplasms - pathology
Stomach Neoplasms - surgery
Surgical Oncology
Survival Rate
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Summary: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.
ISSN:1436-3291
1436-3305
DOI:10.1007/s10120-014-0398-3