Influence of tumor localization on the prognostic value of p53 protein in colorectal adenocarcinomas

Background: The prevalence of genetic alterations is different in primary c arcinomas from the proximal colon when compared with carcinomas from the di stal colorectum. The objective of this work was to explore the existence of possible differences in the informative weight of the risk of tumor recurr ence provided by p53 immunostaining depending on the localization of the ne oplasm. Patients and Methods: Nuclear immunohistochemical expression of p53 protein was determined in formalin-fixed paraffin-embedded archival tumor tissue samples from 190 primary colorectal adenocarcinomas. The relative pr ognostic importance on the risk of recurrence of each variable was assessed in a Cox's proportional hazard regression analysis. Multiplicative interac tion terms between p53 and tumor sire were included in the multivariate mod els in order to test their joint effect on survival. Results: One hundred a nd one patients (53.1%) manifested nuclear accumulation of the protein. P53 overexpression was more frequent in distal than in proximal tumors (58.5% ve s 41.7%) (p=0.03). Disease-free survival was lower in p53-positive cases (75% versus 38%) (p=0.006), but significance of the association varied acc ording to the localization of the tumor (p=0.004 in proximal carcinomas and p=0.049 in distal carcinomas). Multivariate analysis identified p53 positi vity and distal tumor localization as the factors significantly associated with a high risk of recurrence Interaction between p53 expression and local ization was present. P53 exhibited different prognostic value in distal and proximal colon. While adjusted hazard ratio for positive p53 was 1.99 in d istal cancers, it was 8.04 for proximal tumors. Conclusion: The prognostic with value of tumor recurrence associated overexpression of p53 protein is influenced by the location of the tumor The negative predictive weight is s ignificantly higher in proximal than in distal cancers.