PT  - JOURNAL ARTICLE
AU  - RUBIO, CARLOS A.
AU  - RODESJÖ, MARGARETA
AU  - DUVANDER, ANNIKA
AU  - MATHIES, MARIANNE
AU  - GARBERG, LISA
AU  - SHETYE, JAYANT
TI  - p53 Up-regulation During Colorectal Carcinogenesis
DP  - 2014 Dec 01
TA  - Anticancer Research
PG  - 6973--6979
VI  - 34
IP  - 12
4099  - http://ar.iiarjournals.org/content/34/12/6973.short
4100  - http://ar.iiarjournals.org/content/34/12/6973.full
SO  - Anticancer Res2014 Dec 01; 34
AB  - 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.