TP53 AND LONG-TERM PROGNOSIS IN COLORECTAL-CANCER - MUTATIONS IN THE L3 ZINC-BINDING DOMAIN PREDICT POOR SURVIVAL

In a consecutive series of 222 colorectal carcinomas from patients wit h a median follow-up time of 56.8 months (range, 0.5-92.2) treated wit h surgery, the TP53 gene was screened for mutations. Exons 5-8 were an alyzed using constant denaturant gel electrophoresis followed by seque ncing, and mutations were found in 102 cases (45.9%). Mutations were f ound more frequently in rectal tumors versus other locations (P = 0.02 9) and in aneuploid compared to diploid tumors (P < 0.001). Presence o f a TP53 mutation was also significantly associated with absence of mi crosatellite instability (P = 0.028), as well as with loss of heterozy gosity at 17p13 (P < 0.001). The TP53 mutations in the left-sided and rectal tumors were more often transversions than transitions, indicati ng a different etiology in the development of these tumors. The tenden cy for shorter cancer-related survival among patients with mutations i n their tumors was only statistically significant for patients with le ft-sided tumors (P = 0.003). All patients with mutations affecting the L3 domain of the protein involved in zinc binding had a significantly shorter cancer-related survival (P = 0.036), indicating that mutation s affecting this domain have biological relevance in terms of colorect al cancer disease course. These results suggest that knowledge of a pa tient's TP53 status, with respect to both the presence and the localiz ation of the mutation, may be important in prognosis evaluation, parti cularly when selecting patients for more aggressive postoperative ther apeutic intervention.