Increased cell proliferation characterizes Crohn's disease

Patients with long-standing Crohn's disease (CD), a chronic inflammatory in testinal disease, are at increased risk for intestinal cancer. The neoplasi a likely results, in part, from deregulated cell proliferation, which allow s mutations to become fixed in the crypt progenitor cells. We postulated th at tissues derived from patients with CD would exhibit increased mucosal pr oliferation. Therefore we examined specimens from 27 consecutive patients w ith chronic CD with. a monoclonal antibody directed against the proliferati on marker, Ki-67. The tissues were evaluated histologically, and the Ki-67 immunostaining patterns were recorded. The antibody to Ki-67 stained the ba ses of the crypts in both the small and large intestines. The mean number o f Ki-67 immunoreactive cells in the normal crypt was 34.1 versus 95.1 in th e regenerative mucosa and 0 in areas of pyloric metaplasia (P <.00001), KI- 67 staining of the mucosa of patients with CD confirmed that cell prolifera tion is markedly increased and that the replicating compartment, of each cr ypt during regeneration is expanded. We concluded that the increased cell p roliferation might predispose the mucosa to mutational events, thereby incr easing the cancer risk in these patients. The lack of proliferation in area s of pyloric metaplasia might represent a mucosal adaptive response of the lower crypt that decreases the number of cycling cells vulnerable to geneti c damage. Furthermore, growth factors produced by these cells might promote healing of the damaged mucosa.