Caldes T, Iniesta P, Vega F J, de Juan C, Lopez J A, Diaz-Rubio E, Fernandez C, Cerdan J, Balibrea J L, Benito M
Servicio de Immunología, Hospital Universitario San Carlos, Madrid, España.
Oncology. 1998 May-Jun;55(3):249-57. doi: 10.1159/000011859.
Immunohistochemical reactivity for p53 protein is common in various human malignancies. Increased intracellular concentration of p53, which is frequently, but not systematically, related to p53 mutation, has been proposed to be associated with poor prognosis in some tumor types. In colorectal cancer, this significance is still a matter of debate. To directly investigate the relationship between prognosis and p53 alterations, we screened a series of 72 colorectal carcinomas for overexpression and mutation of the p53 gene. Mutations in exons 5-9 of the p53 gene were assayed by single-strand conformation polymorphism and direct DNA sequencing, whereas p53 protein accumulation was detected in 10-microm frozen tissue by immunostaining using 2 different monoclonal antibodies (PAb 1801 and DO7). Thirty-six tumors (50%) showed p53 overexpression. Nineteen of the 36 tumors which contained high levels of p53 protein were found to have missense point mutations. Using a multivariate survival analysis, stage, differentiation, p53 immunoreactivity and p53 mutation emerged as risk factors, but only the stage was significant. In univariate analysis, stage, differentiation and p53 immunoreactivity were significant prognostic indicators, while p53 mutation was at the borderline of significance.
p53蛋白的免疫组化反应性在各种人类恶性肿瘤中很常见。细胞内p53浓度升高常与p53突变有关，但并非总是如此，有人提出在某些肿瘤类型中，这与预后不良有关。在结直肠癌中，这种意义仍存在争议。为了直接研究预后与p53改变之间的关系，我们对72例结直肠癌进行了一系列筛查，以检测p53基因的过表达和突变情况。通过单链构象多态性和直接DNA测序检测p53基因第5至9外显子的突变，而使用两种不同的单克隆抗体（PAb 1801和DO7）进行免疫染色，在10微米厚的冰冻组织中检测p53蛋白的积累情况。36例肿瘤（50%）显示p�3过表达。在36例p53蛋白水平高的肿瘤中，有19例发现有错义点突变。使用多因素生存分析，分期、分化程度、p53免疫反应性和p53突变均为危险因素，但只有分期具有显著性。在单因素分析中，分期、分化程度和p53免疫反应性是显著的预后指标，但p53突变处于显著性临界值。
