Tumour suppressor gene expression correlates with gastric cancer prognosis
Tumour suppressor gene expression correlates with gastric cancer prognosis
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DOI：
10.1002/path.1288
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发表时间：
2003-05-01
影响因子：
7.3
通讯作者：
Kim, WH
中科院分区：
文献类型：
--
作者：
Lee, HS;Lee, HK;Kim, WH
肿瘤抑制基因（tumor suppressor genes，TSGs）的缺失是包括胃癌在内的许多人类癌症的关键事件。已经研究了许多TSG候选物，但它们在胃癌发生中的作用仍不清楚。为了阐明TSG在胃癌中表达的临床意义，（p53、E-钙粘蛋白、FHIT、smad 4、rb、VHL、PTEN、MGMT、p16和KAI 1）以及其他蛋白质（bcl-2、MUC 1、MUC 2、MUC 5AC、MUC 6、CEA、CD 44、β-连环蛋白、C-erbB 2和细胞周期蛋白B2），采用组织芯片法对329例连续胃癌进行免疫组化评价。p53和MUC 1的过度表达（p < 0.01）以及Smad 4（p = 0.04）、FHIT（p = 0.03）、MGMT（p = 0.01）、E-cadherin、KAI 1和PTEN（p < 0.01）的表达缺失与胃癌预后不良显著相关。8种生存相关蛋白中有7种是TSGs的蛋白产物。根据TSG表达的改变程度将胃癌分为五组。32例（TSG 1）未见TSG表达缺失。47例（TSG 2）、67例（TSG 3）、64例（TSG 4）和38例（TSG 5）中分别发现1例、2例、3例或4例TSG丢失。TSG表达的分级与WHO分级（p = 0.04）、pTNM分期、淋巴结浸润和患者生存率（后三者p < 0.01）显著相关。多因素分析显示，TSG表达分级与患者生存率显著相关（P < 0.01）。总之，这项研究的结果表明，TSG表达在胃癌中的累积损失是决定患者生存的重要因素。版权所有（C）2003约翰威利父子有限公司。
The loss of tumour suppressor genes (TSGs) is a key event in many human cancers, including gastric carcinoma. Many TSG candidates have been studied, but their roles in gastric carcinogenesis remain unclear. To clarify the clinical significance of TSG expression in gastric carcinoma, the expression of various TSG candidates (p53, E-cadherin, FHIT, smad4, rb, VHL, PTEN, MGMT, p16, and KAI1), as well as other proteins (bcl-2, MUC1 MUC2, MUC5AC, MUC6, CEA, CD44, beta-catenin, C-erbB2, and cyclin B2), was evaluated immunohistochemically in 329 consecutive gastric carcinomas using the tissue array method. The overexpression of p53 and MUC1 (p < 0.01) and the loss of expression of smad4 (p = 0.04), FHIT (p = 0.03), MGMT (p = 0.01), E-cadherin, KAI1, and PTEN (p < 0.01) were found to be significantly associated with poor gastric carcinoma prognosis. Seven out of eight survival-associated proteins were found to be protein products of TSGs. The gastric carcinomas were divided into five groups according to the grade of alteration in TSG expression. No TSG expression loss was found in 32 cases (TSG1). One TSG loss was found in 47 cases (TSG2), two in 67 cases (TSG3), three or four in 64 cases (TSG4), and five, six, or seven in 38 cases (TSG5). The grade of TSG expression was confirmed to be significantly associated with WHO classification (p = 0.04), pTNM stage, lymphatic invasion, and patient survival (p < 0.01 for the latter three). By multivariate analysis, the grade of TSG expression was found to be significantly and independently associated with patient survival (P < 0.01). In conclusion, the findings of this study suggest that the cumulative loss of TSG expression in gastric carcinoma is important in determining patient survival. Copyright (C) 2003 John Wiley Sons, Ltd.