P53 ALTERATIONS ARE ASSOCIATED WITH IMPROVED PROGNOSIS IN DISTAL COLONIC CARCINOMAS

Alterations of the p53 gene and the p53 protein are common in a wide s pectrum of human malignancies, In several tumor types, p53 gene mutati on and/or p53 protein overexpression correlate with a more clinically aggressive phenotype as judged by worse patient survival. This has not been clearly demonstrated to be the case in colorectal cancer, Herein , we report results of the prognostic significance of p53 protein accu mulation and gene mutation in a large series of colorectal cancers (n = 541) with long patient follow-up (mean, 87 months), The large majori ty of patients (95%) received no postoperative systemic adjuvant thera py, The incidence of p53 accumulation detected by immunohistochemistry with the monoclonal antibody DO-7 was 30%, whereas the incidence of p 53 gene mutation in exons 5-8 detected using PCR-single strand conform ation polymorphism was 36%, Accumulation of p53 protein was associated with improved patient survival independent of tumor stage or grade (h azard ratio, 0.66; 95% confidence interval, 0.47-0.93; P = 0.017), A m arked difference was observed depending on the location of the tumor: tumors originating in the distal colon showed a strong association bet ween the presence of p53 accumulation and improved patient survival (P = 0.003), but this was not the case for those located in the proximal colon, Dukes' stage C tumors, but not stage B, also showed an associa tion between p53 accumulation and better outcome (P = 0.013), Mutation of the p53 gene was associated with a trend toward improved survival, particularly in the distal tumors, Our results demonstrate that in so me tumor types, the presence of p53 abnormalities can correlate with b etter prognosis.