Mechanisms of oncogenesis in colon versus rectal cancer
Mechanisms of oncogenesis in colon versus rectal cancer
复制标题
DOI：
10.1002/path.918
复制
发表时间：
2001-09-01
影响因子：
7.3
通讯作者：
van Krieken, JHJM
中科院分区：
文献类型：
--
作者：
Kapiteijn, E;Liefers, GJ;van Krieken, JHJM
观察结果支持了左侧和右侧结直肠癌的发展可能涉及不同机制的理论。本研究探讨了参与结肠癌和直肠癌发生的不同基因，并分析了它们的预后价值。研究组包括35例结肠癌和42例直肠癌。直肠癌患者接受了由经验丰富的直肠癌外科医生进行的标准化手术治疗。对8例结肠癌中的p53和22例直肠癌中的APC和p53进行突变分析。MLH 1、MSH 2、Bcl-2、p53、E-cadherin和β-catenin在所有结直肠肿瘤中通过免疫组织化学进行研究。MCR的APC突变分析显示，22例直肠肿瘤中有18例（82%）存在截短突变，但APC突变的存在与细胞核β-连环蛋白表达无关（p = 0.75）。直肠癌显示出比结肠癌显著更多的核β-连环蛋白（65%对40%，p = 0.04）。p53突变分析与p53免疫组化结果一致（p < 0.001）。直肠癌的p53免疫组化表达明显高于结肠癌（64%比29%，p = 0.003）。在直肠癌中，p53阳性表达与较差的无病生存率之间存在显著相关性（p = 0.008），但在结肠癌中没有相关性。考克斯回归分析显示，p53表达（p = 0.03）是直肠癌无病生存的独立预测因子。该研究得出结论，直肠癌可能比结肠癌在APC/β-连环蛋白通路中涉及更多的核β-连环蛋白，和/或核β-连环蛋白可能在直肠癌中具有独立于APC的另一种作用。p53通路在直肠癌中似乎更重要，在直肠癌中也具有独立的预后价值。当在更大的系列中研究预后标志物时，应考虑结肠癌和直肠癌之间生物学行为的差异。版权所有（C）2001约翰威利父子有限公司
Observations support the theory that development of left- and right-sided colorectal cancers may involve different mechanisms. This study investigated different genes involved in oncogenesis of colon and rectal cancers and analysed their prognostic value. The study group comprised 35 colon and 42 rectal cancers. Rectal cancer patients had been treated with standardized surgery performed by an experienced rectal cancer surgeon. Mutation analysis was performed for p53 in eight colon cancers and for APC and p53 in 22 rectal cancers. MLH1, MSH2, Bcl-2, p53, E-cadherin and beta -catenin were investigated by immunohistochemistry in all colorectal tumours. APC mutation analysis of the MCR showed truncating mutations in 18 of 22 rectal tumours (82%), but the presence of an APC mutation was not related to nuclear beta -catenin expression (p = 0.75). Rectal cancers showed significantly more nuclear beta -catenin than colon cancers (65% versus 40%, p = 0.04). p53 mutation analysis corresponded well with p53 immunohistochemistry (p < 0.001). Rectal cancers showed significantly more immunohistochemical expression of p53 than colon cancers (64% versus 29%, p = 0.003). In rectal cancers, a significant correlation was found between positive p53 expression and worse disease-free survival (p = 0.008), but not in colon cancers. Cox regression showed that p53-expression (p = 0.03) was an independent predictor for disease-free survival in rectal cancers. This study concluded that rectal cancer may involve more nuclear beta -catenin in the APC/beta -catenin pathway than colon cancer and/or nuclear beta -catenin may have another role in rectal cancer independently of APC. The p53-pathway seems to be more important in rectal cancer, in which it also has independent prognostic value. When prognostic markers are investigated in larger series, differences in biological behaviour between colon and rectal cancer should be considered. Copyright (C) 2001 John Wiley & Sons, Ltd.