Flat adenoma-adenocarcinoma sequence in the colon of rats

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Abstract
As there is an increased awareness of the existence of a "flat adenoma-adenocarcinoma sequence" in the colonic mucosa of human subjects, the aims of the study were to assess whether flat colonic adenocarcinomas in rats are also preceded by flat adenomas, as is reported in humans, and to determine the frequency of flat lesions compared with exophytic lesions in the colon of rats. The colonotropic carcinogen 1,2-dimethylhydrazine was injected subcutaneously in 300 Sprague-Dawley rats for 27 weeks. A total of 358 tumors developed in 278 of the 300 rats. Of the 60 adenomas found at histology, 25 percent were flat adenomas. Of the 298 adenocarcinomas, 12.7 percent had originated in a flat adenoma. Of the 180 colonic neoplasias (adenomas or adenocarcinomas), 29.4 percent were flat neoplasias (flat adenomas or adenocarcinomas arising in a flat adenoma), and the remaining 70.6 percent were exophytic neoplasias (tubulo or villous adenomas or adenocarcinomas arising in exophytic adenomas). From the 298 colonic adenocarcinomas, 1 was a intramucosal adenocarcinoma, 87 were overt adenocarcinomas, and 90 were lymphoid-associated carcinomas; in those 298 adenocarcinomas, no preneoplastic lesion could be recorded. In 208 animals, biopsies were taken from macroscopically visible colonic lesions, and, in the remaining 70 animals, the entire colon was processed for histologic examination. Flat adenomas were found in 3.8 percent of the 208 biopsy specimens and in 10 percent of the 70 colectomy specimens. Further, of the 40 adenomas found in biopsy specimens, 20 percent were flat adenomas, and, of the 20 adenomas found in colectomy specimens, 35 percent were flat adenomas. The study reported herein indicates 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 seen 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 lesions. Consequently, flat adenomas may be overlooked by naked-eye examination.