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A “field change” of inhibited apoptosis occurs in colorectal mucosa adjacent to colorectal adenocarcinoma
  1. S Badvie1,
  2. A Hanna-Morris1,
  3. H J N Andreyev2,
  4. P Cohen3,
  5. S Saini1,
  6. T G Allen-Mersh1
  1. 1Department of Surgery, Chelsea & Westminster Hospital, London, UK
  2. 2Department of Medicine, Chelsea & Westminster Hospital, Imperial College London, London, UK
  3. 3Faculty of Medicine, Department of Histopathology, Charing Cross Hospital, Imperial College London, London, UK
  1. Correspondence to:
    S Badvie
    Department of Academic Surgery, Chelsea & Westminster Hospital, 369 Fulham Road, London SW10 9NH, UK; sara.badvie{at}doctors.org.uk

Abstract

Background: Colorectal cancer is associated with a “field change” of increased proliferation throughout the colonic and rectal mucosa. Both proliferation and apoptosis are disrupted during carcinogenesis. Whether altered apoptosis contributes to this field change of microscopic abnormality is, however, unclear. Bcl-xL is an anti-apoptotic protein that inhibits apoptosis by preventing release of cytochrome c, a recognised pathway to cell death.

Aim: To determine whether Bcl-xL inhibition of apoptosis is increased in colorectal mucosa adjacent to colorectal adenocarcinoma over that in normal non-neoplastic colorectal mucosa.

Patients: Patients undergoing surgical resection for neoplastic (adenocarcinoma) or non-neoplastic disease of the colorectum (rectal prolapse, diverticular disease or volvulus).

Methods: Formalin-fixed, paraffin-wax-embedded surgical colorectal resection specimens were immunostained for Bcl-xL protein. Labelling indices were determined by counting the proportion of positively stained cells in mucosal crypts.

Results: 85 patients were studied. Bcl-xL immunostaining was most marked in the upper third of mucosal crypts. It occurred in a minority of samples from non-neoplastic colorectal mucosa, but was seen in most mucosal samples adjacent to colorectal adenocarcinoma. Significant increases (p<0.001) were observed in Bcl-xL labelling indices in the mucosa at 1 cm (n = 46, median labelling index 31.8%, interquartile range 8.3–43.9%) and at 10 cm (n = 52, median labelling index 22.0%, interquartile range 0.0–36.3%) from colorectal carcinoma, compared with normal, non-neoplastic colorectal mucosa (n = 22, median labelling index 0.0%, interquartile range 0.0–0.0%).

Conclusions: The findings are consistent with a field change of inhibited apoptosis in mucosa adjacent to colorectal carcinoma.

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Footnotes

  • Published Online First 5 May 2006

  • Competing interests: None.

  • Ethical approval: This study was approved by the Riverside Ethics Committee, London.

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