p53 up-regulation during colorectal carcinogenesis

We previously found foci of p53 up-regulation in dysplasia in colorectal adenomas (CRAs). The present study aimed at exploring the frequency of this phenomenon in CRAs with and without submucosal invasive carcinoma.

Sections from 568 polypectomies or surgical resections harbouring a CRA (without or with submucosal invasion) or overt colorectal carcinomas were challenged with p53 immunostaining. The largest section from single colorectal neoplasias was measured by the aid of a calibrated ocular scale in a conventional microscope. Lesions were divided into small adenomas (≤10 mm in size), large adenomas (≥11 mm in size), adenomas with submucosal invasion, and overt invasive carcinomas (without any recognizable adenoma remnant tissue).

CRAs with three or more dysplastic foci of p53-up-regulation gradually increased from 8% in small adenomas (size: ≤10 mm) to 48% in large adenomas (size: ≥11 mm), and to 65% in the adenomatous tissue in adenomas displaying submucosal invasion), but plummeted to 13% in the submucosal carcinomatous tissue and to 11% in overt carcinomas. In contrast, extensive p53 up-regulation predominated in the submucosal carcinomatous tissue (87%) and in overt carcinomas (89%).

The frequency of foci of dysplastic glands with up-regulation of p53 (hotspots) gradually increased from small to larger CRAs, being highest in the adenomatous tissue of CRAs with submucosal invasive carcinoma. The foci of p53 up-regulation became confluent (appreciated as extensive up-regulation) in the submucosal carcinomatous tissue and in overt carcinomas. It is concluded that a high number of foci with p53 up-regulation in adenomatous tissue might be required before submucosal invasive carcinoma ensues.