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KMID : 0939920030350020109
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대한암학회지
2003 Volume.35 No. 2 p.109 ~ p.116
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The Prognostic Significance of the Overexpression of HER-2/ neu in Korean Gastric Carcinomas and the In Vitro Effects of Anti-HER-2/neu Antibody on Cell Growth in the Gastric Carcinoma Cell Lines
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Im Seock-Ah
Lee Kyong-Eun
Nam Eun-Mi
Nam Seung-Hyun
Kim Do-Yeun
Seong Chu-Myong
Park Hae-Young
Han Woon-Sup
Seoh Ju-Young
Lee Soon-Nam
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Abstract
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Purpose: The HER2 gene encodes a 185-kd transmembrane glycoprotein receptor (p185HER2) that has partial homology with the epidermal growth factor receptor (EGFR) and shares intrinsic tyrosine kinase activity. The HER2 gene has been found to be amplified in various human cancers and to be associated with poor prognosis. The authors investigated the correlation between clinicopathologic factors and the overexpression of the p185HER2 in Korean gastric adenocarcinoma patients, and determined whether the antiproliferative effects of anti- p185HER2 antibody can also be observed on gastric cancer cell lines that overexpress this growth factor receptor.
Materials and Methods: We evaluated the relationship between p185HER2 overexpression and clinicopathological features in 94 (M갌F=52갌42) gastric adenocarcinoma patients (median age 59 years). Protein expression was analysed by immunohistochemical staining in paraffin embedded tissues with monoclonal antibody for p185HER2. To explore the role of humanized anti-p185HER2 monoclonal antibody trastuzumab (HerceptinⰒ) in vitro, the growth curve of Korean gastric cancer cells that overexpress the p185HER2 protein was studied and a cell cycle analysis was performed.
Results: p185HER2 overexpression correlates positively with lymph node metastasis (p=0.002), distant metastasis
(p=0.01), AJCC classification (p=0.01), higher relapse rate
(p=0.001), and a tendential association with the pT stage (p=0.054). p185HER2 overexpression was found to be more frequent in advanced gastric cancer than early gastric cancer (54.1% vs 24.2%, p=0.008). Patients with overexpression of p185HER2 were found to have significantly lower relapse-free (p=0.003) and overall survival (p= 0.0004) than patients without overexpression. Among several Korean gastric cancer cell lines, SNU-1, SNU-5, and SNU-620 overexpress p185HER2. Trastuzumab inhibited the proliferation of p185HER2 overexpressed Korean gastric cancer cell line by 21% with down-regulation of p185HER2 protein expression. DNA fluorescence flow cytometry of propidium iodide-stained nuclei showed a reduction in the fraction of the S phase following treatment with trastuzumab.
Conclusions: Taken together, our observations suggest the potential prognostic significance of p185HER2 overexpression in Korean gastric adenocarcinoma patients and point to the need for further research on this mechanism. This suggests the possible use of p185HER2 as a therapeutic target in gastric cancer. (Cancer Research and Treatment 2003;35:109-116)
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KEYWORD
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p185HER2, Prognostic factor, Stomach neoplasm, Trastuzumab
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