p53 protein overexpression in colorectal tumors from patients with familial adenomatous polyposis: Is it an early or late event?

Objectives: Tumor development is a multistep process associated with multiple genetic alterations. Familial adenomatous polyposis (FAP) is a classical paradigm to study genetic alterations in the development of colorectal neoplasms. In this study, we investigated the timing of p53 overexpression by immunohistochemistry in colorectal carcinogenesis in FAP patients and in sporadic adenomas and adenocarcinomas. Methods: We examined 40 microadenomas, 114 tubular adenomas, and three adenocarcinomas from five FAP patients and 30 sporadic adenomas and 14 sporadic adenocarcinomas. Results: p53 overexpression was observed in 43 of 114 adenomas with mild and moderate dysplasia and in three of three adenocarcinomas and in none of 40 microadenomas from FAP patients. In sporadic tumors, six of 30 adenomas with moderate to severe dysplasia and 11 of 14 carcinomas showed p53 overexpression. Uninvolved colonic mucosa in FAP patients, control patients, and patients with sporadic tumors did not stain for p53. Conclusions: These results indicate that p53 overexpression occurs early in the development of colorectal adenomas in FAP, whereas it is a late event in the development of sporadic tumors.