title: HER-2/neu amplification is an independent prognostic factor in gastric cancer.
abstract: The HER-2/neu protein is intimately involved with normal cell proliferation and tissue growth and is extensively homologous and related to the epidermal growth factor receptor. HER-2/neu protein expression has been most intensively studied in the context of breast carcinoma, in which its amplification and overexpression correlate with the overall course of disease, and with a poor prognosis, and constitute a predictive factor of poor response to chemotherapy and endocrine therapy. In this study, we investigated the relationship between the expression of HER-2/neu and the clinicopathological characteristics of tumors, including survival. This study was performed with a view toward the future introduction of Herceptin therapy for gastric cancer patients. HER-2/neu overexpression and gene amplification was examined with semiquantitative standardized immunohistochemical staining, chromogenic in situ hybridization (CISH), and fluorescence in situ hybridization (FISH) in 182 gastric cancer patients who underwent curative surgery at the Kangbuk Samsung Hospital. Twenty-nine (15.9%) of 182 patients expressed the HER-2/neu protein by immunohistochemistry. HER-2/neu gene amplification was detected in seven patients by CISH and FISH. Intestinal-type cancers exhibited higher rates of HER-2/neu amplification than did diffuse-type cancers (P < 0.05). Tumors with HER-2/neu amplification were associated with poor mean survival rates (922 vs 3243 days) and 5-year survival rates (21.4% vs 63.0%; P < 0.05). Age, TNM stage, and amplification of HER-2/neu were found to be independently related to survival by multivariate analysis. HER-2/neu amplification may constitute an independent prognostic factor in gastric cancer patients, and patients exhibiting HER-2/neu amplification might constitute potential candidates for new adjuvant therapies which involve the use of humanized monoclonal antibodies.
authors.affiliation: Department of Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Dong Il
authors.initials: DI
authors.lastname: Park
authors.forename: Jung Won
authors.initials: JW
authors.lastname: Yun
authors.forename: Jung Ho
authors.initials: JH
authors.lastname: Park
authors.forename: Suk Joong
authors.initials: SJ
authors.lastname: Oh
authors.forename: Hong Joo
authors.initials: HJ
authors.lastname: Kim
authors.forename: Yong Kyun
authors.initials: YK
authors.lastname: Cho
authors.forename: Chong Il
authors.initials: CI
authors.lastname: Sohn
authors.forename: Woo Kyu
authors.initials: WK
authors.lastname: Jeon
authors.forename: Byung Ik
authors.initials: BI
authors.lastname: Kim
authors.forename: Chang Hak
authors.initials: CH
authors.lastname: Yoo
authors.forename: Byung Ho
authors.initials: BH
authors.lastname: Son
authors.forename: Eun Yoon
authors.initials: EY
authors.lastname: Cho
authors.forename: Seoung Wan
authors.initials: SW
authors.lastname: Chae
authors.forename: Eo-Jin
authors.initials: EJ
authors.lastname: Kim
authors.forename: Jin Hee
authors.initials: JH
authors.lastname: Sohn
authors.forename: Seung Ho
authors.initials: SH
authors.lastname: Ryu
authors.forename: Antonia R
authors.initials: AR
authors.lastname: Sepulveda
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor; D002277:Carcinoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D004273:DNA, Neoplasm / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005784:Gene Amplification; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; D018719:Erb-b2 Receptor Tyrosine Kinases