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  • Severe imbalance of cell proliferation and apoptosis in the left colon and in the rectosigmoid tract in subjects with a history of large adenomas

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Gastrointestinal cancer
Severe imbalance of cell proliferation and apoptosis in the left colon and in the rectosigmoid tract in subjects with a history of large adenomas
  1. M Antia,
  2. A Armuzzia,
  3. S Morinid,
  4. E Iasconea,
  5. G Pignataroa,
  6. C Cocob,
  7. R Lorenzettie,
  8. M Paoluccia,
  9. M Covinoa,
  10. A Gasbarrinia,
  11. FM Vecchioc,
  12. G Gasbarrinia
  1. aDepartment of Internal Medicine, Catholic University of Rome, Rome, Italy, bDepartment of Surgery, Catholic University of Rome, Rome, Italy, cDepartment of Pathology, Catholic University of Rome, Rome, Italy, dNuovo Regina Margherita Hospital, Rome, Italy, eSan Giacomo Hospital, Rome, Italy
  1. Dr M Anti, Department of Internal Medicine, Catholic University of Rome, Largo F. Vito, 1, 00168 Rome, Italy. antimar{at}tin.it

Abstract

BACKGROUND Alterations in epithelial proliferation and apoptosis in colonic mucosa are associated with an increased risk of colon cancer. It is unclear if these alterations represent a generalised “field defect”.

AIMS To analyse segmental patterns of cell proliferation and apoptosis in the colon of subjects with a high and no apparent risk of colon cancer.

METHODS Pancolonoscopy was performed in 15 patients with resected adenomas (⩾1.5 cm) and in nine subjects without an apparent risk of colorectal cancer. Mucosal biopsies were taken from the right colon, left colon, and sigmoid rectum. Crypt cell proliferation and apoptosis were evaluated, respectively, with bromodeoxyuridine immunohistochemistry and terminal deoxyuridine nucleotidyl nick end labelling of DNA strand breaks. Results are expressed as total labelling index (TLI) and labelling index (LI) for each of the five compartments in which colonic crypts were divided (fourth and fifth compartments were evaluated together) for cell proliferation and as apoptotic index (AI) for apoptosis assessment.

RESULTS No significant segmental variations in proliferation were found in either group. Compared with controls, adenoma patients had higher TLIs for the right (p>0.05), left (p<0.005), and sigmoid rectum (p<0.05) segments, and higher left colon LIs for crypt compartments (compartment 1, p<0.01; compartment 2, p<0.005; compartment 3, p<0.001; compartments 4–5, p<0.01). Control AIs were similar in all segments but in the adenoma patients left colon and sigmoid rectum AIs were lower than their right colon indexes (p<0.05, p<0.05) and corresponding values for controls (p<0.01, p<0.05).

CONCLUSIONS The colonic mucosa of patients with past adenomas presents diffuse hyperproliferation and, distally, abnormally distributed proliferating cells and markedly reduced apoptosis. These changes represent a significant risk for malignancies and could account for the high prevalence of left colon tumours.

  • cell proliferation
  • apoptosis
  • colon cancer risk

  • Abbreviations used in this paper

    ACF
    aberrant crypt foci
    AI
    apoptotic index
    APC
    adenomatous polyposis coli
    BrdU
    bromodeoxyuridine
    BSA
    bovine serum albumin
    DAB
    diaminobenzidine
    dUTP
    deoxyuridine triphosphate
    HNPCC
    hereditary non-polyposis colorectal cancer
    LI
    labelling index
    PBS
    phosphate buffered saline
    PEG
    polyethylene glycol solution
    TdT
    terminal deoxynucleotidyl transferase
    TLI
    total labelling index
    TUNEL
    TdT mediated dUTP-biotin nick end labelling

    • https://doi.org/10.1136/gut.48.2.238

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    • Abbreviations used in this paper

      ACF
      aberrant crypt foci
      AI
      apoptotic index
      APC
      adenomatous polyposis coli
      BrdU
      bromodeoxyuridine
      BSA
      bovine serum albumin
      DAB
      diaminobenzidine
      dUTP
      deoxyuridine triphosphate
      HNPCC
      hereditary non-polyposis colorectal cancer
      LI
      labelling index
      PBS
      phosphate buffered saline
      PEG
      polyethylene glycol solution
      TdT
      terminal deoxynucleotidyl transferase
      TLI
      total labelling index
      TUNEL
      TdT mediated dUTP-biotin nick end labelling
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