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

• Published in: Gut Vol. 48; no. 2; pp. 238 - 246
• Main Authors: Anti, M, Armuzzi, A, Morini, S, Iascone, E, Pignataro, G, Coco, C, Lorenzetti, R, Paolucci, M, Covino, M, Gasbarrini, A, Vecchio, FM, Gasbarrini, G
• Format: Journal Article
• Language: English
• Published: London BMJ Publishing Group Ltd and British Society of Gastroenterology 01.02.2001; BMJ; BMJ Publishing Group Ltd; BMJ Publishing Group LTD
• Subjects: Adenoma; Adenoma - pathology; Adenoma - physiopathology; Adult; Aged; Analysis of Variance; Antigens; Apoptosis; Apoptosis - physiology; Biological and medical sciences; Biopsy; Bromodeoxyuridine; Case-Control Studies; Cell death; Cell Division - physiology; Cell growth; Cell proliferation; colon cancer risk; Colorectal cancer; Colorectal Neoplasms - pathology; Colorectal Neoplasms - physiopathology; Diagnosis; Digestive system; Equilibrium; Female; Hospitals; Humans; In Situ Nick-End Labeling; Intestinal Mucosa - pathology; Investigative techniques, diagnostic techniques (general aspects); Labeling; Male; Medical sciences; Middle Aged; Normal distribution; Oncology; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques; Physiology; Population; Rodents; Statistics, Nonparametric; Surveillance; Tumors; Human; Mucosa; Cytology; Cell biology; Histology; Adenoma; Proliferation; Carcinogenesis; Colonic disease; Pathology; Phenotype; Pelvic colon; Risk factor; Digestive diseases; Epithelial cell; Benign neoplasm; Biological effect; Left colon; Comparative study; Apoptosis
• ISSN: 0017-5749; 1468-3288; 1458-3288
• DOI: 10.1136/gut.48.2.238

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.