title: p53 up-regulation during colorectal carcinogenesis.
abstract: 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.
  
  
  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%).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pathology, Karolinska Institute and University Hospital, Stockholm, Sweden Carlos.Rubio@ki.se.
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Rubio
authors.affiliation: Department of Pathology, Karolinska Institute and University Hospital, Stockholm, Sweden.
authors.forename: Margareta
authors.initials: M
authors.lastname: Rodesjö
authors.affiliation: Department of Pathology, Karolinska Institute and University Hospital, Stockholm, Sweden.
authors.forename: Annika
authors.initials: A
authors.lastname: Duvander
authors.affiliation: Department of Pathology, Karolinska Institute and University Hospital, Stockholm, Sweden.
authors.forename: Marianne
authors.initials: M
authors.lastname: Mathies
authors.affiliation: Department of Pathology, Karolinska Institute and University Hospital, Stockholm, Sweden.
authors.forename: Lisa
authors.initials: L
authors.lastname: Garberg
authors.affiliation: Department of Pathology, Karolinska Institute and University Hospital, Stockholm, Sweden.
authors.forename: Jayant
authors.initials: J
authors.lastname: Shetye
mesh_terms: D011125:Adenomatous Polyposis Coli / Q000378:metabolism / Q000473:pathology*; D063646:Carcinogenesis / Q000378:metabolism* / Q000473:pathology; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D009361:Neoplasm Invasiveness; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis*; D015854:Up-Regulation
chemical_list: D016159:Tumor Suppressor Protein p53
keywords: Colorectal adenomas; focal up-regulation; invasive carcinoma; p53