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.
Barrett's esophagus is thought to progress to esophageal adenocarcinoma (EAC) through a stepwise progression with loss of CDKN2A followed by TP53 inactivation and aneuploidy.
Frequent somatic mutations in the tumor suppressor genes CDKN2A and TP53 were recently reported in EA tumors, while somatic alterations at 9p (CDKN2A) and 17p (TP53) have been implicated as predictors of progression from BE to EA.
Following co-culture with visceral adipose tissue explants, expression of genes involved in tumour cell invasion and metastasis (matrix metalloproteinase (MMP)2 and MMP9) were upregulated between 10-fold (MMP2) and 5000-fold (MMP9), and expression of tumour suppressor p53 was downregulated 2-fold in OAC cell lines.
The aim of the study was to evaluate expression, prognostic value and correlation between COX-2 and VEGF expression in esophageal adenocarcinoma (EAC).
Indomethacin and parecoxib inhibit the growth of human esophageal adenocarcinoma xenografts in nude mice, which suggests a potential role for NSAIDs or selective COX-2 inhibitors for EAC chemotherapy.
The role of cyclooxygenase-2 (COX-2) and chronic inflammation in the progression of BE toward adenocarcinoma of the esophagus has not been extensively studied in experimental models of BE in animals and in human subjects.
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.
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 p53 mutations are a predictor of significantly reduced postoperative survival following surgical resection of EADC, and would appear to be a clinically useful molecular prognostic biomarker.
No significant differences were found for patients with EADC who had p53 mutations (n = 21) compared with patients with wild-type p53 (n = 33) with respect to selected clinicopathologic variables (age, gender, tumor grade, stage, alcohol, or tobacco consumption) and dietary intake of folate or vitamin B(6).
The results suggest that silencing of ARF is involved in the pathogenesis of oesophageal adenocarcinoma and show that either DNA or histone methylation can provide the primary mechanism for ARF gene silencing.
We have determined the p16 mutation spectrum for a cohort of 304 patients with Barrett's esophagus, a premalignant condition that predisposes to the development of esophageal adenocarcinoma.
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.
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.
At 10 y, all abnormalities, except CDKN2A mutation and methylation, contributed to EA risk significantly by univariate analysis, ranging from 17p LOH (relative risk [RR] = 10.6; 95% confidence interval [CI] 5.2-21.3, p < 0.001) to 9p LOH (RR = 2.6; 95% CI 1.1-6.0, p = 0.03).