Correlation between malignancy grade and p53 gene in relation to thymidine phosphorylase activity in colorectal cancer patients.

We studied 89 colorectal cancer patients conducting immunohistological staining of thymidine phosphorylase (TP) and investigated correlation between the enzyme activity levels, clinicopathologic factors and patient prognosis. Based on TP expression level, we also assessed p53, an anti-oncogene related to hematogenesis and nucleic acid metabolism. TP staining results were classified into: i) strongly stained group (8 patients) in which 20% or more tumor cell nuclei were stained and ii) weakly stained group (39 patients) in which less than 20% of the nuclei were stained. These 2 groups were defined as TP positive group and those without TP staining (42 patients) were defined as TP negative group. TP positive group showed: a significantly higher incidence of vascular infiltration (p=0.0065) than TP negative group, and slightly higher incidence of lymphatic permeation and tumor progress. Strongly stained group showed significantly higher incidences of vascular infiltration and lymphatic permeation (p=0.0001, p=0.0271). As for 5-year survival rate, TP positive group showed a significantly lower rate (29%) than TP negative group (52%) (p=0.05) indicating that TP expression level was an important prognostic factor in colorectal cancer patients. No differences were found in pathologic factors and patient prognosis between groups with or without point mutation. As for relationship between TP staining and p53, there were significantly more patients with strongly positive TP staining in the p53 negative group. These findings suggest that TP is an important prognostic factor for colorectal cancer patients, and p53, in conjunction with other factors, is also a prognostic indicator.