There has been few reports describing that the prognostic significance of p53 alteration in colorectal tumors depended on the site of origin. Therefore, in this study, we examined whether there is a valid association between the p53 alterations and the prognosis of colorectal cancer patients, especially distal colorectal cancer cases. Tumor samples were collected from 110 patients resected for colorectal cancer between 1989 and 1997. The entire coding region of the p53 gene was analyzed by automated direct sequencing. In addition, the DO-7 monoclonal antibody was used in the immunohistochemical (IHC) assessments. By the Cox univariate analyses in all tumors, Dukes' stage, lymph node metastasis, liver metastasis, p53 mutation and p53 protein overexpression were significant predictors of survival. The cases without p53 mutation showed significantly improved prognosis compared to the cases with p53 mutation (p=0.0085). In distal tumors, Dukes' stage, liver metastasis, p53 mutation and p53 protein overexpression were significant predictors of survival. Multivariate analysis of all tumors, p53 mutation and liver metastasis were independent indicators of poor survival (p=0.0223 for p53 mutation, p=0.0254 for liver metastasis). Also in distal tumors, p53 mutation was an independent indicator (p=0.0011). Furthermore, the relative risk associated with p53 mutation in distal tumors was much higher than that in all tumors (8.260 vs. 1.796). However, p53 protein overexpression was not an independent indicator of survival in all tumors as well as distal tumors (p=0.1918 in all tumors, p=0.0607 in distal tumors). In proximal tumors, p53 mutation was not an independent indicator (p=0.6673). We think that p53 mutation is a very useful prognostic indicator when distal colorectal cancers are considered.

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