FLAT ADENOMA-ADENOCARCINOMA SEQUENCE IN THE COLON OF RATS

PURPOSE: As there is an increased awareness of the existence of a ''fl at adenoma-adenocarcinoma sequence'' in the colonic mucosa of human su bjects, the aims of the study were to assess whether nat colonic adeno carcinomas in rats are also preceded by flat adenomas, as is reported in humans, and to determine the frequency of hat lesions com pared wit h exophytic lesions in the colon of rats. METHOD: The colonotropic car cinogen 1,2-dimethylhydrazine was injected subcutaneously in 300 Sprag ue-Dawley rats for 27 weeks. RESULTS: A total of 358 tumors developed in 278 of the 300 rats. Of the 60 adenomas found at histology, 25 perc ent a ere hat adenomas. Of the 298 adenocarcinomas, 12.7 percent had o riginated in a flat adenoma. Of the 180 colonic neoplasias (adenomas o r adenocarcinomas), 29.4 percent were nat neoplasias (flat adenomas or adenocarcinomas arising in a nat adenoma), and the remaining 70.6 per cent were exophytic neoplasias (tubulo or villous adenomas or adenocar cinomas arising in exophytic adenomas). From the 298 colonic adenocarc inomas, 1 was a intramucosal adenocarcinoma, 87 were overt adenocarcin omas, and 90 were lymphoid-associated carcinomas; in those 298 adenoca rciaomas, no preneoplastic lesion could be recorded. In 208 animals, b iopsies were taken from macroscopically visible colonic lesions, and, in the remaining 70 animals, the entire colon was processed for histol ogic examination. Flat adenomas were found in 3.8 percent of the 208 b iopsy specimens and in 10 percent of the 70 colectomy specimens. Furth er, of the 40 adenomas found in biopsy specimens, 20 percent were nat adenomas, and, of the 20 adenomas found in colectomy specimens, 35 per cent were flat adenomas. CONCLUSIONS: The study reported herein indica tes the existence of a ''flat adenoma-adenocarcinoma sequence'' in the colonic mucosa of Sprague-Dawley rats. The flat lesions of the colon constituted approximately one-third of the total neoplastic lesions se en in the rat following injections of 1,2-dimethylhydrazine. More flat adenomas were detected at histologic examination of the entire colon than in biopsies obtained from the macroscopically visible colonic les ions. Consequently, flat adenomas may be overlooked by naked-eye exami nation.