In a population-based case-control study, we examined associations of the COX-2 8473 T>C and iNOS Ser(608) Leu (C>T) polymorphisms with risk of esophageal adenocarcinoma, Barrett's esophagus, and reflux esophagitis.
Abnormal p16 expression (negative, cytoplasmic, or combined cytoplasmic and nuclear staining) was present in all categories, rising from 68% in BE without dysplasia to 100% in AdenoCa, with cytoplasmic staining only showing a significant correlation with the severity of dysplasia.
Patients with OAC and TP53 gene mutations have reduced overall survival compared with patients without these mutations, and this effect is independent of tumour stage.
COX-2 inhibition induces apoptosis and blocks proliferation in COX-2-expressing esophageal adenocarcinoma cells in vitro, and blocks angiogenesis in both in vivo and in vitro models.
We also correlated COX-2 and FGF-2 expression with clinico-pathologic findings and outcome in a well-characterized series of surgically resected EADC tissues.
The incidence of oesophageal adenocarcinoma is rising; to date, no susceptibility genes have been identified. p73, a novel p53 homologue, maps to chromosome 1p36, a region commonly deleted in oesophageal cancers. p73 shares some p53-like activity, but in addition, may also play a role in gastrointestinal epithelial inflammatory responses.
These results confirm the important role of Cox-2 amplification in the pathogenesis of esophageal adenocarcinoma, but the unexpected down-regulation of Cox-1 raises questions about its role in carcinogenesis.
Therefore, we examined whether acid increases methylation of p16 gene promoter and whether NADPH oxidase NOX5-S mediates acid-induced p16 hypermethylation in a Barrett's cell line BAR-T and an EA cell line OE33.
Esophageal adenocarcinoma is characterized by evolution of punctuated and catastrophic somatic chromosomal alterations and high levels of overall mutations but few recurrently mutated genes aside from TP53.
The COX-2 enzyme has been reported to be over-expressed in premalignant and malignant states, including in Barrett's esophagus and esophageal adenocarcinoma.
17p (TP53) loss of heterozygosity (LOH) has been reported to be predictive of progression from Barrett's esophagus to esophageal adenocarcinoma, but the mechanism by which TP53 LOH develops is unknown.
In subgroup analyses based on pathological type, the Pro variant was significantly associated with an increased esophageal squamous cell carcinoma (ESCC) risk in all four genetic comparison models (ORPro vs. Arg=1.26, 95% CI: 1.08-1.47, POR=0.003; OR Recessive genetic model=1.42, 95% CI: 1.07-1.88, POR=0.015; ORDominant genetic model=1.25, 95% CI: 1.10-1.42, POR=0.001; ORHomozygote model=1.55, 95% CI: 1.14-2.10, POR=0.005), whereas the association between TP53Arg72Pro polymorphism and esophageal adenocarcinoma risk was still uncertain owing to the limited studies included in this meta-analysis.
The two types of tumor differed in the prevalence of TP53 mutations (31% in ADCC and 50% in ADCE) and of MDM2 gene amplification (19% in ADCC and 4% in ADCE), and in the pattern of expression of cytokeratin 7 (positive in 100% of ADCE and in 41% of ADCC) and cytokeratin 13 (positive in 81% of ADCE and in 36.5% of ADCC).
To investigate the role of NO in esophageal adenocarcinoma (EADC), we studied patterns of p53 mutations, expression of inducible nitric oxide synthase (iNOS) and the tissue accumulation of nitrotyrosine (NTS), a stable reaction product of NO and a marker for cellular protein damage, in human premalignant and malignant esophageal epithelia.