Laser capture microdissection and in situ hybridization analysis show almost exclusive expression of Dio2 in the stroma of Apc<sup>Δ716</sup> polyps in the proximity of the COX-2-positive areas.
The Cysltr1-/- colonic polyps exhibited significant decreases in nuclear β-catenin and COX-2 protein expression, while the normal crypts surrounding the polyps exhibited increased Mucin 2 expression.
Furthermore, any (1+/2+) COX-2 overexpression was more frequent in non-serrated adenomas (60% = 307/515) than in hyperplastic polyps (13% = 3/24, p < 0.0001) and serrated polyps (SSAs and mixed polyps) (25% = 3/12, p = 0.03).
Results suggest that use of NSAIDs is associated with lower levels of COX-2 expression and that the protective effect of NSAIDs on polyp occurrence is stronger in the subgroup of cases with higher expression of COX-2 and a higher COX-2/COX-1 ratio.
Additionally, treatment with COX-2-selective inhibitors reduces polyp burden in animal models of intestinal neoplasia and in humans with familial adenomatous polyposis (FAP).
Reactive intermediates formed during the arachidonic acid cascade, notably by COX-2, which is upregulated in polyps of FAP patients, may promote various stages of the polyp --> adenoma --> carcinoma sequence.
However, COX-2 mRNA expression in nasal polyps from the AIAR group (0.38 +/- 0.10) was markedly and significantly lower than in polyps from the ATAR group (2.93 +/- 0.
Offspring from cox-2 null by Apcdelta716 matings exhibit an 86% reduction in polyp number when compared to offspring from control animals, thus providing genetic evidence that COX-2 contributes to tumor formation or growth.