Experimental adenomas and carcinomas of the large intestine behave as distinct entities: Most carcinomas arisede novo in flat mucosa

Abstract

Detailed histologic analyses were performed on tumors of the large intestine obtained in 152 dimethylhydrazine (DMH)-treated rats. Of a total 539 glandular neoplasms, 45 were benign; 494 (92%) were locally invasive; of which 222 (41%) were invading the muscularis propria. One-hundred-forty-one tumors were smaller than or equal to 3mm in diameter. Among those, 127 (90%) were invasive. In addition to macroscopic nodules, several appeared after longer latency periods than did serial sections of flat mucosa. The benign polyps usually appeared after longer latency periods than did carcinomas. A review of the literature indicates that in the majority of rat experiments most or all DMH-induced tumors were frequently reported. All these data constitute strong evidence that most experimental adenocarcinomas do arise de novo in flat mucosa, i.e., without a prior adenoma stage. However, most DMH-induced tumors in mice were reported to be adenomas, either alone or coexisting with carcinomas. It is suggested that "de novo arising carcinomas" and adenomatous polyps, which are both inducible by the same carcinogens, and which can coexist in some experimental systems, nonetheless constitute independent and distinct pathologic entities; they can be separated by genetic susceptibility.

Early colorectal cancer: concept, diagnosis, and management

“…De-novo carcinogenesis from flat mucosa, without going through an adenomatous stage, is not rare in the gastrointestinal tract, other than the colorectum. Studies of chemically induced colonic carcinomas in experimental animals 23,24 have shown evidence in support of de-novo carcinogenesis. It is only in the human colorectum that the adenoma-carcinoma sequence is regarded as the main pathway of carcinogenesis.…”

Experimental control of neoplastic progression in cell populations: Foulds' rules revisited.

“…It was later pointed out that many, ifnot most colonic cancers, arise in non-polyp-bearing colons (26), so the dual origin of these tumors is likely. In the rat, most experimental cancers ofthe large intestine arise de novo in the flat mucosa without prior adenomatous change (27). The adenoma-carcinoma sequence is more common in mice, but some strains exhibit a predominance of cancer without adenomas (28).…”

Fluorescence localization of early colonic cancer in the rat by hematoporphyrin derivative

“…We did not observe adenomas in this study. Indeed, there is evidence that the adenoma/carcinoma sequence does not occur in rats given DMH [18] or its active metabolite, azoxymethane [191. Laser induced fluorescence (LIF) of colonic lesions without photosensitizing agents has been recently suggested as a method of distinguishing neoplastic from hypergreat utility in the screening and diagnosis of co- lonic polyps.…”