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RAS和p53在预测杜克B期结直肠癌患者生存率中的作用

ras and p53 in the prediction of survival in Dukes' stage B colorectal carcinoma.

作者信息

Bennett M A, Kay E W, Mulcahy H, O'flaherty L, O'donoghue D P, Leader M, Croke D T

机构信息

Department of Biochemistry, Royal College of Surgeons in Ireland, Dublin, Ireland.

出版信息

Clin Mol Pathol. 1995 Dec;48(6):M310-5. doi: 10.1136/mp.48.6.m310.

Abstract

Aims-To determine possible associations between p53 allelic deletion, c-Ki-ras mutational activation, immunohistochemical detection of p53 and ras proteins, various clinicopathological variables, and patient outcome in 168 Dukes' stage B colorectal carcinomas.Methods-Allelic deletion at the p53 tumour suppressor gene locus was detected using polymerase chain reaction (PCR) based loss of heterozygosity (LOH) assays. Overexpressed proteins were detected using the CM1 polyclonal antibody. A PCR based assay was used to detect the presence of activating mutations at codon 12 of c-Ki-ras. Immunostaining was carried out using a monoclonal antibody to p21(ras).Results-p53 LOH, CM1 immunostaining, c-Ki-ras mutational activation, and p21(ras) immunostaining were not predictive of survival by logrank analysis. Multivariate analysis using Cox regression did not predict survival in this group of tumours.Conclusions-Aberrations in ras and p53 are unlikely to play an important role in the subdivision of patients with Dukes' stage B colorectal carcinoma into more accurate prognostic strata. It is possible that later genetic events are more important in conferring a specific phenotype on the resultant Dukes' stage B tumour.

摘要

目的——确定168例杜克B期结直肠癌中p53等位基因缺失、c-Ki-ras突变激活、p53和ras蛋白的免疫组化检测、各种临床病理变量与患者预后之间的可能关联。方法——使用基于聚合酶链反应(PCR)的杂合性缺失(LOH)分析检测p53肿瘤抑制基因位点的等位基因缺失。使用CM1多克隆抗体检测过表达的蛋白。使用基于PCR的分析检测c-Ki-ras第12密码子激活突变的存在。使用抗p21(ras)单克隆抗体进行免疫染色。结果——通过对数秩分析,p53 LOH、CM1免疫染色、c-Ki-ras突变激活和p21(ras)免疫染色均不能预测生存情况。使用Cox回归进行的多变量分析也不能预测这组肿瘤患者的生存情况。结论——ras和p53的异常在将杜克B期结直肠癌患者细分为更准确的预后分层中不太可能起重要作用。在赋予所得杜克B期肿瘤特定表型方面,后期遗传事件可能更重要。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0460/407996/fa045863b2c7/clinmolpath00011-0025-a.jpg

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