We retrospectively analyzed the 5mC content of 42 patients with intestinal metaplasia (a precancerous lesion of GC) treated with a COX-2 specific inhibitor Rofecoxib or placebo for 2 years, revealing that the COX-2 inhibitor significantly down-regulated 5mC levels (N=42, P=0.009).
Concerning about the origin of p63/p40 and CDX2, it was suggested that the tumor cells were not derived from ectopic squamous epithelium but from intestinal metaplasia.
Previous studies indicated that SOX2, the key transcription factor in gastric differentiation, was downregulated during IM development while CDX2, the pivotal intestine-specific transcription factor was upregulated significantly.
Intestinal-type gastric cancer often results from <i>Helicobacter pylori</i> infection through intestinal metaplasia, a transdifferentiated premalignant phenotype.Because <i>H. pylori</i> virulence factor CagA has been associated with aberrant expression of the transcription factor CDX1, which regulates intestinal differentiation, we explored its relationship with <i>H. pylori</i> infection and function during gastric carcinogenesis in normal gastric epithelial cells and gastric cancer cell lines.
Conversely, of the 47 patients initially negative forCDX-2, 8 (17.9%) developed goblet cell IM after 24 months and only 11 (23.8%) after 40 to 45 months (P = .049; age-adjusted Cox proportional hazard regression model).
SATB2 in combination with CDX2 and CK20 differentiates sinonasal ITAC from non-ITAC with increased diagnostic sensitivity and specificity and detects IM in the sinonasal tract more easily.
The COX-2 1195 G-carrier genotype was also significantly (p = 0.038) associated with the score of endoscopic intestinal metaplasia based on Kyoto classification.
Morphological changes, mRNA, and protein expression levels for the inflammatory marker cyclooxygenase-2; the lineage-determining transcription factors TAp63 (squamous), CDX2, and SOX9 (both columnar); and the columnar lineage markers Villin, Muc-2, CK8, and mAb Das-1 (incomplete phenotype of intestinal metaplasia) were assessed every 10 wk.
It can be speculated that either CDX2 positive morula formation or intestinal metaplasia of the endometrium as rare conditions might be the origin of carcinogenesis for this type II endometrial cancer.
Morphological changes, mRNA, and protein expression levels for the inflammatory marker cyclooxygenase-2; the lineage-determining transcription factors TAp63 (squamous), CDX2, and SOX9 (both columnar); and the columnar lineage markers Villin, Muc-2, CK8, and mAb Das-1 (incomplete phenotype of intestinal metaplasia) were assessed every 10 wk.
Morphological changes, mRNA, and protein expression levels for the inflammatory marker cyclooxygenase-2; the lineage-determining transcription factors TAp63 (squamous), CDX2, and SOX9 (both columnar); and the columnar lineage markers Villin, Muc-2, CK8, and mAb Das-1 (incomplete phenotype of intestinal metaplasia) were assessed every 10 wk.
CDX2 is a crucial factor in the development of pre-cancerous lesions such as Barrett's esophagus or intestinal metaplasia in the stomach, and its tumor suppressive role has been investigated in colorectal cancers.
These data suggest that NKX6.3 might function as a master regulator of gastric differentiation by affecting SOX2 and CDX2 expression and the NKX6.3 inactivation may result in intestinal metaplasia in gastric epithelial cells.
ISX expression induced by H. pylori infection may lead to IM and hyperproliferation of gastric mucosa through CDX1/2 and cyclinD1 expression, contributing to gastric carcinogenesis.
No significant association between COX-2 methylation and risk of progression to GC was found in subjects with IM (OR, 0.50; 95% CI: 0.18-1.42) or DYS (OR, 0.70; 95% CI: 0.23-2.18).
Further, we identified increased protein expression of Mdm2/x, both powerful regulators of p53, in 100% of the IM+GC cohort with these samples also exhibiting high levels of wild-type p53 protein.
Methylation of the Cdx2 promoter was not observed in intestinal metaplasia, while hypermethylation of part of its promoter was observed in hot dipped and IMC.
Even in the patients without IM regression, the mean IM scores and COX-2 expressions were significantly more decreased in the celecoxib group than in the controls (p < .005).