p27 downregulation and metallothionein overexpression in gastric cancer patients are associated with a poor survival rate
p27 downregulation and metallothionein overexpression in gastric cancer patients are associated with a poor survival rate
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DOI：
10.1002/jso.20402
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发表时间：
2006-03-01
影响因子：
2.5
通讯作者：
De Vita, F
中科院分区：
文献类型：
--
作者：
Galizia, G;Ferraraccio, F;De Vita, F
背景和目的：由于大量经过治愈的胃癌患者最终会复发，因此迫切需要研究新的预后标志物来识别高危患者。在本研究中，我们探讨了参与细胞周期调节（B1和D3细胞周期蛋白和p27）和细胞保护（金属硫蛋白，MT）的分子标志物在预测胃癌患者肿瘤行为和临床结局中的可能作用。方法：对73例胃癌患者样本和25例正常胃粘膜标本进行免疫组化分析上述指标。结果： 正常胃粘膜细胞显示 B1 和 D3 细胞周期蛋白和 MT 的低表达，以及强烈的 p27 染色。相反，胃肿瘤细胞表现出较高的细胞周期蛋白D3和MT，以及较低的p27表达。 B1 细胞周期蛋白的表达在正常组织和肿瘤组织之间没有差异。 p27 和 MT 表达在几乎所有癌症样本中都发生改变，并且与肿瘤进展密切相关。原发肿瘤的晚期范围、淋巴结转移、低 p27 和高 MT 表达是预测不良临床结果的最佳变量组合。每个标记物预测的结果都比基于肿瘤淋巴结 (TNM) 系统的分期更好。随着分子改变的增加，生存率和复发率下降。最后，分子谱测定正确预测了具有相同 TNM 分期的患者的预后。结论：p27 和 MT 表达与临床结果密切相关，从而可以识别可能受益于定制治疗的不利患者群体。 B1 和 D3 细胞周期蛋白在胃癌中的作用仍有待阐明。
Background and Objectives: As a significant number of curatively treated gastric cancer patients will ultimately relapse, there is an urgent need to investigate new prognostic markers for identification of high-risk patients. In this study, we investigated the possible role of molecular markers involved in cell cycle regulation (B1 and D3 cyclins, and p27) and cell protection (metallothionein, MT) in predicting tumor behavior and clinical outcome in gastric cancer patients.Methods: Analysis of the above indicators was performed by immunohistochemistry on 73 gastric cancer patient samples and 25 normal gastric mucosa specimens.Results: Normal gastric mucosa cells displayed low expressions of B1 and D3 cyclins and MT, and intense p27 staining. Conversely, gastric tumor cells showed higher cyclin D3 and MT, and lower p27 expressions. B1 cyclin expressions were not different between normal and tumor tissue. p27 and MT expressions were altered in almost all cancer samples, and were strongly correlated with tumor progression. Advanced extent of the primary tumor, nodal metastasis, low p27, and high MT expressions were the best combination of variables for prediction of poor clinical outcome. Each marker predicted outcome better than staging based on tumor-node (TNM) system. Survival and recurrence rates decreased as molecular alterations increased. Finally, molecular profile determination correctly predicted the prognosis in patients with same TNM stage.Conclusions: p27 and MT expressions strongly correlated with clinical outcome allowing to identify an unfavorable group of patients that may benefit from tailored treatments. The role of B1 and D3 cyclins in gastric cancer remains to,be elucidated.