Gut-associated lymphoid tissue and dimethylhydrazine-induced colorectal carcinoma in the Wistar/Furth rat

Abstract

Although gut-associated lymphoid tissue in the form of discrete lymphoid patches (LP-GALT) in mammalian intestine in most prominent in the distal ileum, appendix, and, in some species, the cecal appendage, LP-GALT can be found throughout the intestinal tract. LP-GALT appears as single or multiple subepithelial lymphoid follicles covered by a specialized, structurally unique epithelium. In the colon of the Wistar/Furth (W/Fu) rat, LP-GALT appears as aggregates of follicles, or lymphoid patches, that can be detected macroscopically. We studied the relationship between 1,2-dimethylhydrazine- (DMH) induced colon carcinomas and the lymphoid patch associated epithelium in these animals. In addition, we defined the normal distribution of colonic lymphoid patches in both DMH-treated and control rats. Patches were found macroscopically and confirmed by histologic examination at five constant sites: lower pole of cecum, proximal ascending colon, the major colonic flexure, mid descending colon, and the rectosigmoid. There are also the predominant sites of DMH induced carcinomas in W/Fu rats. In 120 DMH-treated animals, 109 colon carcinomas were found. Eight percent were in the lower pole of the cecum, 56% in the proximal ascending colon, 16% at the major flexure, 15% in the mid descending colon, and 5% in the rectosigmoid. Lymphoid patches could often be detected histologically in association with DMH-induced tumors. The depth of tumor invasion was found to correlate inversely with our ability to identify tumor-associated lymphoid patches suggesting that tumors arising at the anatomical sites were lymphoid patches occur progressively destroyed them. Of colon tumors confirmed histologically to be associated with lymphoid patches, 88% were superficial lesions confined to the submucosa and 12% were more extensive but confined to the bowel wall. No lymphoid patches could be found associated with tumors that extended through the bowel wall. Thus, DMH-induced colon carcinomas in W/Fu rats arise at sites containing preexisting LP-GALT with associated specialized epithelium.