Smith D R, Ji C Y, Goh H S
Department of Colorectal Surgery, Singapore General Hospital, Singapore.
Br J Cancer. 1996 Jul;74(2):216-23. doi: 10.1038/bjc.1996.340.
The p53 tumour-suppressor gene is found altered in the majority of colorectal cancers. Lesions include allelic loss, mutation of the gene and overexpression of the p53 protein. All of these lesions have been analysed for prognostic significance, and whereas both mutation and allelic loss have been shown to be reasonably useful markers of prognosis, the utility of overexpression of the p53 protein is more ambiguous. Given that many authors use p53 overexpression as a marker for point mutation this issue is of some importance. We have therefore examined 100 colorectal carcinomas for mutation of the p53 gene, as well as overexpression of the p53 protein. Results show that whereas mutation of the p53 gene is associated with p53 overexpression, the degree of association depends, at least in part, upon the particular antibody used. Moreover, although mutation of the p53 gene does provide prognostic information, overexpression of the p53 protein, as detected with two antibodies, does not. These results suggest that immunohistochemistry is not a suitable alternative to direct detection of mutation in assessing prognosis in colorectal cancer patients.
在大多数结直肠癌中发现p53肿瘤抑制基因发生改变。病变包括等位基因缺失、基因的突变以及p53蛋白的过表达。所有这些病变都已进行了预后意义分析,虽然已经表明突变和等位基因缺失都是相当有用的预后标志物,但p53蛋白过表达的效用却更为模糊。鉴于许多作者将p53过表达用作点突变的标志物,这个问题具有一定重要性。因此,我们检测了100例结直肠癌的p53基因突变以及p53蛋白的过表达情况。结果表明,虽然p53基因突变与p53过表达相关,但关联程度至少部分取决于所使用的特定抗体。此外,尽管p53基因突变确实能提供预后信息,但用两种抗体检测到的p53蛋白过表达却不能。这些结果表明,在评估结直肠癌患者预后时,免疫组化并非直接检测突变的合适替代方法。