TY - JOUR T1 - p53 Up-regulation During Colorectal Carcinogenesis JF - Anticancer Research JO - Anticancer Res SP - 6973 LP - 6979 VL - 34 IS - 12 AU - CARLOS A. RUBIO AU - MARGARETA RODESJÖ AU - ANNIKA DUVANDER AU - MARIANNE MATHIES AU - LISA GARBERG AU - JAYANT SHETYE Y1 - 2014/12/01 UR - http://ar.iiarjournals.org/content/34/12/6973.abstract N2 - Background: 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. Materials and Methods: 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). Results: 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%). Conclusion: 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. ER -