HER-2/neu amplification is an independent prognostic factor in gastric cancer
HER-2/neu amplification is an independent prognostic factor in gastric cancer
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DOI：
10.1007/s10620-005-9057-1
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发表时间：
2006-08-01
影响因子：
3.1
通讯作者：
Sepulveda, Antonia R.
中科院分区：
文献类型：
--
作者：
Park, Dong Il;Yun, Jung Won;Sepulveda, Antonia R.
HER-2/neu蛋白与正常细胞增殖和组织生长密切相关，并且与表皮生长因子受体广泛同源和相关。HER-2/neu蛋白表达在乳腺癌中的研究最为深入，其中其扩增和过表达与疾病的总体过程相关，并且具有不良预后，并且构成对化疗和内分泌治疗的不良反应的预测因素。在这项研究中，我们调查HER-2/neu的表达和肿瘤的临床病理特征，包括生存之间的关系。本研究的目的是为了将来在胃癌患者中引入赫赛汀治疗。HER-2/neu过度表达和基因扩增进行了半定量标准化免疫组化染色，显色原位杂交（CISH），荧光原位杂交（FISH）在182例胃癌患者接受根治性手术在江北三星医院。免疫组化检测HER-2/neu蛋白阳性率为15.9%（29/182）。CISH和FISH检测7例HER-2/neu基因扩增。肠型癌HER-2/neu扩增率高于弥漫型癌（P < 0.05）。HER-2/neu扩增的肿瘤与低的平均生存率（922 vs 3243天）和5年生存率（21.4% vs 63.0%; P < 0.05）相关。多因素分析发现年龄、TNM分期和HER-2/neu扩增与生存率独立相关。HER-2/neu扩增可能构成胃癌患者的独立预后因素，并且表现出HER-2/neu扩增的患者可能构成涉及使用人源化单克隆抗体的新辅助治疗的潜在候选者。
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.