Kressner U, Inganäs M, Byding S, Blikstad I, Påhlman L, Glimelius B, Lindmark G
Department of Surgery, University Hospital, Pharmacia Biotech AB, Uppsala, Sweden.
J Clin Oncol. 1999 Feb;17(2):593-9. doi: 10.1200/JCO.1999.17.2.593.
To explore whether there is a linkage between different mutations in the p53 gene in primary colorectal cancer and the risk of death from colorectal cancer in a large group of patients with long follow-up. We also compared a complementary DNA-based sequencing method and an immunohistochemical (IHC) method for detecting p53 protein overexpression in colorectal cancer.
The entire coding region of the p53 gene was sequenced in 191 frozen tumor samples collected from January 1988 to November 1992. RNA was extracted and synthesized to cDNA. p53 was amplified by the polymerase chain reaction, and the DO-7 monoclonal antibody was used in the IHC assessments.
Mutations were detected in 99 samples (52%) from 189 patients. There was a significant relationship between the p53 mutational status and the cancer-specific survival time, with shorter survival time for patients who had p53 mutations than for those who did not (P = .01, log-rank test). Mutations outside the evolutionarily conserved regions were associated with the worst prognosis. Multivariate analysis showed that the presence of p53 mutations was an independent prognostic factor (relative hazard, 1.7, P = .03). There was no significant relationship between overexpression of p53 protein, as determined by IHC analysis, and cancer-specific survival.
Mutational analyses of the p53 gene, using cDNA sequencing in colorectal cancer, provide useful prognostic information. In addition, cDNA sequencing gives better prognostic information than IHC assessment of p53 protein overexpression.
探讨在一大组随访时间长的原发性结直肠癌患者中，p53基因的不同突变与结直肠癌死亡风险之间是否存在联系。我们还比较了基于互补DNA的测序方法和免疫组织化学（IHC）方法检测结直肠癌中p53蛋白过表达的情况。
对1988年1月至1992年11月收集的191份冷冻肿瘤样本的p53基因整个编码区进行测序。提取RNA并合成为cDNA。通过聚合酶链反应扩增p53，并在IHC评估中使用DO-7单克隆抗体。
在189例患者的99份样本（52%）中检测到突变。p53突变状态与癌症特异性生存时间之间存在显著关系，p53突变患者的生存时间短于未突变患者（P = .01，对数秩检验）。进化保守区域外的突变与最差的预后相关。多变量分析表明，p53突变的存在是一个独立的预后因素（相对风险，1.7，P = .03）。通过IHC分析确定的p53蛋白过表达与癌症特异性生存之间无显著关系。
在结直肠癌中使用cDNA测序对p53基因进行突变分析可提供有用的预后信息。此外，cDNA测序比p53蛋白过表达的IHC评估能提供更好的预后信息。
