Increased p53 protein content of colorectal tumours correlates with poor survival.
Increased p53 protein content of colorectal tumours correlates with poor survival.
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结直肠肿瘤的 p53 蛋白含量增加与生存率低相关。
DOI：
10.1038/bjc.1992.352
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发表时间：
1992-10
影响因子：
8.8
通讯作者：
Thomas, G
中科院分区：
文献类型：
--
作者：
Remvikos, Y;Tominaga, O;Hammel, P;Laurent-Puig, P;Salmon, R J;Dutrillaux, B;Thomas, G
17号染色体短臂上的等位基因丢失经常发生在结直肠癌中。尽管存在其他常见的分子事件，如18号和5号染色体长臂的丢失，但已证明前者具有最大的预后意义。在定位于常见缺失序列的各种基因中，作为“靶”的最佳候选基因似乎是p53抗癌基因。我们应用我们的方法检测p53蛋白在一系列的78个结直肠癌储存在肿瘤银行从1985年至1989年，中位随访时间为42个月。流式细胞术定量检测细胞核粘附的p53，ELISA检测可溶性p53。两种测定法均使用了被认为对仅存在于突变蛋白上的构象表位具有特异性的单克隆抗体。78个肿瘤中的50个（64%）被发现存在显著水平的p53附着于细胞核。另外两个肿瘤仅在其可溶性部分中含有高水平的p53。因此，78种癌症中有52种（67%）被认为是p53阳性。p53含量与17 p丢失（P < 0.002）、超二倍体DNA含量（P < 0.001）和肿瘤部位（P < 0.03）相关，而与Dukes分期无关（P = 0.15）。p53阴性组总生存率明显高于p53阳性组（P < 0.03）。当14例D期肿瘤被排除在分析之外时，p53不再显著预测生存（P < 0.07），但仍然预测复发（P < 0.02）和转移（P < 0.03）。由于病例数量较少，未进行多变量分析。总体而言，将无疾病和无转移生存期与使用pAb 421和/或1801或pAb 240获得的阳性进行比较，因为所有三种均用于流式细胞术分析，定义了421-、1801+和421-、1801-、240+的子集。核蛋白呈现突变特异性表位的存在，由pAb 240识别，被认为是最具鉴别力的。必须注意的是，单变量生存分析表明，超过80%的p53阴性肿瘤患者在3年时存活，而p53阳性组的存活率低于50%。应进行大规模的前瞻性研究，以确定结直肠癌p53含量的确切预后意义。
Allelic losses on the short arm of chromosome 17 occur frequently in colorectal cancers. Despite the existence of other common molecular events such as loss of the long arms of chromosomes 18 and 5, it has been demonstrated that the former has the greatest prognostic significance. Of the various genes mapping to the commonly deleted sequence, the best candidate as a 'target' seems to be the p53 antioncogene. We applied our methods of detection of the p53 protein in a series of 78 colorectal cancers stored in a tumour bank from 1985 to 1989, for which the median follow-up was 42 months. Nuclear-attached p53 was quantified by flow cytometry and soluble p53 was assayed by ELISA. Both assays used a monoclonal antibody considered to be specific for a conformational epitope present only on the mutated protein. Fifty of the 78 tumours (64%) were found to present significant levels of p53 attached to the nucleus. A further two tumours contained high levels of p53 only in their soluble fraction. Thus, 52 out of 78 cancers (67%) were considered to be positive for p53. The p53 content correlated with 17p loss (P < 0.002), hyperdiploid DNA content (P < 0.001) and tumour site (P < 0.03), but not Dukes' stage (P = 0.15). p53 negative cases had a better overall survival than p53 positive ones (P < 0.03). When the 14 stage D tumours were excluded from the analysis, p53 was no longer significantly predictive of survival (P < 0.07), but remained predictive of recurrence (P < 0.02) and metastasis (P < 0.03). Multivariate analysis was not performed because of the small number of cases. Overall, disease-free and metastasis-free survival were compared to the positivity obtained either with pAb 421 and/or 1801 or pAb 240 since all three were used in the flow cytometric analysis, defining subsets of 421-, 1801+ and 421-, 1801-, 240+. The presence of nuclear protein presenting the mutation-specific epitope, recognised by pAb 240, was found to be the most discriminant. It must be noted that univariate survival analysis demonstrated that more than 80% of patients with p53-negative tumours were alive at 3 years vs less than 50% in the p53-positive group. A large prospective study should be conducted to define the exact prognostic significance of the p53 content of colorectal carcinomas.