Abstract
Patients from a hereditary nonpolyposis colorectal cancer (HNPCC) kindred (Lynch Type 1 and Type 2) have an increased risk of developing large-bowel cancer. Tumors occur at a young age and are characteristically right-sided. Colonic mucosal proliferation is known to be increased in several groups of patients at risk of colorectal cancer. PURPOSE: This study was performed to assess the pattern of mucosal proliferation at different sites in the colon of patients at risk of HNPCC and to determine whether this pattern differs from normal patients. METHODS: Mucosal biopsies were obtained at colonoscopy from 21 patients at risk for HNPCC (16 females; mean age, 42 years) and from 7 normal patients (4 females; mean age, 38 years), and mucosal proliferation was quantified using the whole crypt mitotic count (WCMC) technique. RESULTS: In patients from HNPCC families, WCMC and crypt area were significantly greater in the cecum than in the transverse colon and left colon (P < 0.001). Compared with normal patients, WCMC in HNPCC patients was significantly greater in the cecum only (P < 0.05). A significant right-to-left shift was also observed in normal patients, but the percentage increase from right to left was two-fold greater in HNPCC patients. CONCLUSIONS: These results confirm a proximalto-distal proliferative gradient in the human colon and suggest that this may be exaggerated in HNPCC. This increased proximal proliferative rate may be a factor in the development of right-sided cancer in these patients.
Similar content being viewed by others
References
Lynch HT, Schuelke GS, Kimberling WJ,et al. Hereditary nonpolyposis colorectal cancer (Lynch syndromes I and II). II. Biomarker studies. Cancer 1985;56:939–51.
Chung DC, Rustgi AK. DNA mismatch repair and cancer. Gastroenterology 1995;109:1685–99.
Deschner EE. Early proliferative changes in gastrointestinal neoplasia. Am J Gastroenterol 1982;77:207–11.
Terpstra OT, van Blankenstein M, Dees J, Eilers GA. Abnormal pattern of cell proliferation in the entire colonic mucosa of patients with colon adenoma or cancer. Gastroenterology 1987;92:704–8.
Welberg JW, de Vries EG, Hardonk MJ,et al. Proliferation rate of colonic mucosa in normal subjects and patients with colonic neoplasms: a refined immunohistochemical method. J Clin Pathol 1990;43:453–6.
Vasen HF, Mecklin J-P, Khan PM, Lynch HT. The International Colaborative Group on Hereditary Non-Polyposis Colorectal Cancer (ICG-HNPCC). Dis Col Rectum 1991;34:424–5.
Lipkin M, Newmark H. Effect of added dietary calcium on colonic epithelial-cell proliferation in subjects at high risk for familial colonic cancer. N Engl J Med 1985;313:1381–4.
Goodlad RA, Levi S, Lee CY, Mandir N, Hodgson H, Wright NA. Morphometry and cell proliferation in endoscopic biopsies: evaluation of a technique. Gastroenterology 1991;101:1235–4l.
Pohl A, Weyant J, Ahnen DJ. Validation of the whole crypt mitotic count (WCMC) as a measure of proliferation in the rat colon. Gastroenterology 1992;102:A939.
Hall C, Youngs D, Keighley MR. Crypt cell production rates at various sites around the colon in Wistar rats and humans. Gut 1992;33:1528–31.
Cooke T, Kirkham N, Stainthorp DH, Inman C, Goeting N, Taylor I. Detection of early neoplastic changes in experimentally induced colorectal cancer using scanning electron microscopy and cell kinetic studies. Gut 1984;25:748–55.
Author information
Authors and Affiliations
Additional information
Supported by the Joint Research Board, St Bartholomew's Hospital, London, United Kingdom.
About this article
Cite this article
Patchett, S.E., Alstead, E.M., Saunders, B.P. et al. Regional proliferative patterns in the colon of patients at risk for hereditary nonpolyposis colorectal cancer. Dis Colon Rectum 40, 168–171 (1997). https://doi.org/10.1007/BF02054982
Issue Date:
DOI: https://doi.org/10.1007/BF02054982