Galizia Gennaro, Ferraraccio Francesca, Lieto Eva, Orditura Michele, Castellano Paolo, Imperatore Vincenzo, La Manna Giovanni, Pinto Margherita, Ciardiello Fortunato, La Mura Anna, De Vita Ferdinando
Division of Surgical Oncology, F. Magrassi-A. Lanzara Department of Clinical and Experimental Medicine and Surgery, Second University of Naples School of Medicine, Naples, Italy.
J Surg Oncol. 2006 Mar 1;93(3):241-52. doi: 10.1002/jso.20402.
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.
Analysis of the above indicators was performed by immunohistochemistry on 73 gastric cancer patient samples and 25 normal gastric mucosa specimens.
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.
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.
由于大量接受根治性治疗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以识别高危患者。在本研究中，我们调查了参与细胞周期调控（B1和D3细胞周期蛋白，以及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方面的可能作用。
通过免疫组织化学对73例胃癌患者样本和25例正常胃黏膜标本进行上述指标分析。
正常胃黏膜细胞显示B1和D3细胞周期蛋白以及MT的低表达，p27染色强烈。相反，胃肿瘤细胞显示细胞周期蛋白D3和MT较高，p27表达较低。正常组织和肿瘤组织之间B1细胞周期蛋白表达无差异。几乎所有癌症样本中p27和MT表达均发生改变，且与肿瘤进展密切相关。原发肿瘤晚期、淋巴结转移、低p27和高MT表达是预测不良临床结局的最佳变量组合。每个标志物对结局的预测均优于基于肿瘤-淋巴结-转移（TNM）系统的分期。随着分子改变增加，生存率和复发率降低。最后，分子谱测定正确预测了相同TNM分期患者的预后。
p27和MT表达与临床结局密切相关，能够识别可能从个体化治疗中获益的不良患者组。B1和D3细胞周期蛋白在胃癌中的作用仍有待阐明。
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