Regional proliferative patterns in the colon of patients at risk for hereditary nonpolyposis colorectal cancer

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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. 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. 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. 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. These results confirm a proximal-to-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.