Can the clinical outcome in stage II colon carcinomas be predicted by determination of molecular marker expression?

Can the clinical outcome in stage II colon carcinomas be predicted by determination of molecular marker expression?
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DOI:
10.1007/s12094-007-0119-z
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发表时间:
2007-10-01
影响因子:
3.4
通讯作者:
Fernandez, M. Ramos
Fernandez, M. Ramos
中科院分区:
医学4区
文献类型:
--
作者:
Fernandez-Cebrian, J. M.;Santos, M. Nevado;Fernandez, M. Ramos

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背景:传统的分期方法往往不能准确预测结肠癌(CC)的预后。在这项研究中,我们着手调查的分子/结构指标参与细胞周期调控(Ki-67,p53),细胞凋亡(p53和bcl-2)和肿瘤新生血管(抗VIII因子)在预测肿瘤的行为和临床结果在第二阶段CC患者的可能作用。实验设计:通过免疫组化对162例接受根治性手术的CC患者样本进行上述指标的分析。临床病理资料包括肿瘤分级、血管和神经浸润、粘液产生、淋巴管渗透和癌胚抗原水平。结果如下:p53蛋白过表达占58%,bcl-2蛋白过表达占21.5%,Ki-67蛋白过表达占60.1%,抗Ⅷ因子染色阳性占40.16%。多元回归分析表明,部分分子标记之间存在相关性。p53与Ki-67、bcl-2与p53之间存在显著相关性,而bcl-2与Ki-67的过度表达之间无相关性。逐步回归选择Ki-67和抗VIII因子作为能够预测疾病特异性和无病生存的变量的最佳组合。结论:只有Ki-67和抗VIII因子被证明是有用的预后和复发率的预测在治愈治疗的CC患者。与临床和病理分期相结合,它们可以提供比单独分期更强的临床结果指示,并有助于更好地选择CC患者的治疗方案。
Background: Conventional staging procedures are often unable to precisely predict prognosis in colon cancer (CC). In this study, we set out to investigate the possible role of molecular/structural indicators involved in cell cycle regulation (Ki-67, p53), apoptosis (p53 and bcl-2) and tumour neoangiogenesis (anti-VIII factor) in predicting tumour behaviour and clinical outcome in stage II CC patients. Experimental design: Analysis of the above indicators was performed by immunohistochemistry on 162 CC patient samples with curative intention surgery. Clinicopathological data included tumour grade, vascular and nervous invasion, production of mucin, lymphatic permeation and carcinoembryonic antigen levels. Results: p53 protein was overexpressed in 58%, bcl-2 overexpression in 21.5%, Ki-67 in 60.1% and anti-VIII factor stained positive in 40.16% of the cases. Multiple regression analysis showed that some molecular markers were correlated. A significant relationship was seen between p53 and Ki-67, and bcl-2 and p53, but there was no correlation between bcl2 and Ki-67 overexpression. Stepwise regression selected Ki-67 and anti-VIII factor as the best combination of variables capable of predicting both disease-specific and disease-free survival. Conclusions: Only Ki-67 and anti-VIII factor were shown to be useful for the prediction of outcome and recurrence rate in curatively treated CC patients. In conjunction with clinical and pathological staging, they may provide a stronger indication of clinical outcome than staging alone and help better select therapeutic options in CC patients.