Association of COX‐2 expression with corresponding active and chronic inflammatory reactions in Barrett's metaplasia and progression to cancer

Ling, Frederike C.; Baldus, Stephan; Khochfar, J.; Hao, Xi Shan; Neiss, Susanne; Brabender, Jan; Metzger, Ralf; Drebber, U.; Dienes, Hans Peter; Bollschweiler, E.; Hoelscher, Arnulf H.; Schneider, Paul M.

doi:10.1111/j.1365-2559.2007.02576.x

Cited by 16 publications

(12 citation statements)

References 35 publications

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“…Theoretically, the difference between COX-2 expression and Met expression as prognostic indicators can probably be explained by their function. The COX-2 enzyme is enhanced in inflammation and has been shown to be involved in early progression of oesophageal metaplasia and dysplasia into (adeno-) carcinoma (Morris et al, 2001;Buskens et al, 2002;Abdalla et al, 2004;Ling et al, 2007). Increased COX-2 expression causes activation of several cancer-related genes including the HGF receptor Met (Boon et al, 2004;Han et al, 2006).…”

Section: Discussionmentioning

confidence: 99%

Met expression is an independent prognostic risk factor in patients with oesophageal adenocarcinoma

et al. 2008

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Oesophageal adenocarcinoma is an aggressive malignancy with propensity for early lymphatic and haematogenous dissemination. Since conventional TNM staging does not provide accurate prognostic information, novel molecular prognostic markers and potential therapeutic targets are subject of intense research. The aim of the present study was to study the prognostic significance of Met, the hepatic growth factor (HGF) receptor and a possible target for therapy in comparison to cyclooxygenase-2 (COX-2). Tumour sections from 145 consecutive patients undergoing intentionally curative surgery for oesophageal adenocarcinoma were immunohistochemically analysed for Met and COX-2 expression. Clinicopathological data were prospectively collected for all patients. Patients with high Met expression had significantly reduced overall and disease-specific 5-year survival rates (Pp0.001 and Pp0.001, respectively) and were more likely to develop distant metastases (P ¼ 0.002) and local recurrences (P ¼ 0.004) compared to patients with low Met expression. High COX-2 expression tended to be correlated with poor long-term survival but this did not reach statistical significance. Expression of Met was recognised as a significant and independent prognostic factor by stage-specific analysis and multivariate analysis (relative risk ¼ 2.3; 95% CI ¼ 1.3 -4.1). These findings support the importance of Met in oesophageal adenocarcinoma and support the concept of Met tyrosine kinase inhibition as (neo-) adjuvant treatment.

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Section: Discussionmentioning

confidence: 99%

Met expression is an independent prognostic risk factor in patients with oesophageal adenocarcinoma

et al. 2008

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“…Some investigators have reported the absence of COX-2 immunostaining in normal epithelium (20,21,28,36) . Our results agree with those reported by JACKSON et al (17) who observed COX-2 expression in normal gastric mucosa.…”

Section: A B C Dmentioning

confidence: 99%

Evaluation of the immunoexpression of COX-1, COX-2 and p53 in Crohn's disease

Romero

Artigiani

Costa

et al. 2008

Arq. Gastroenterol.

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-Background -Crohn's disease accompanied by nonspecific or idiopathic ulcerative proctocolitis corresponds to a condition called intestinal inflammatory disease. The immunoexpression of cyclooxygenase 2 (COX-2) in Crohn's disease becomes more marked with progression of the disease and the presence of wild-type p53 suppresses the transcription of COX-2. Aims -To investigate the immunoexpression of cyclooxygenase 1 (COX-1), COX-2 and p53 in Crohn's ileocolitis and to correlated this expression with clinical and histopathological parameters. Methods -Forty-five cases of Crohn's disease, 16 cases of actinic colitis (diseased-control group) and 11 cases without a history of intestinal disease (normal control group) were studied. Hematoxylin-eosin-stained sections were submitted to histopathological analysis and the immunohistochemical expression of COX-1, COX-2 and p53 was evaluated by the streptavidin-biotin-peroxidase method. Results -Sixty percent of the Crohn's disease patients were women and 40% were men, with 75.5% whites and 25.5% non-whites. The disease involved the terminal ileum in 44.5% of cases, ileum in 33.3%, colon in 20% and duodenum-ileum in 2.2%. A significant association was observed between COX-2 immunoreactivity and age ≤40 years. Histopathological analysis of Crohn's disease samples showed mild or moderate crypt distortion (57.8% and 35.6% of cases), atrophy (6.6%), mild, moderate and marked chronic inflammation (46.7%, 26.7% and 20%), acute inflammatory activity (93.3%), ulceration (24.4%), mucin depletion (37.8%), Paneth's cells (24.4%), intraepithelial lymphocytes (93.3%), and subepithelial collagen (6.7%). In the CD group, COX-1 immunoreactivity in epithelial and inflammatory cells was observed in 26.7% and 22.2% of cases, respectively.

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“…At the histological level, its defining feature is the presence of goblet cells, similar to those of the epithelium of the small intestine and colon. Barrett's metaplasia is characterized by active as well as chronic inflammation [11] suggesting that inflammation contributes to the BE field defect.…”

Section: Esophageal Adenocarcinomamentioning

confidence: 99%

Field defects in progression to gastrointestinal tract cancers

Bernstein

Payne

et al. 2008

Cancer Letters

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A field of defective tissue may represent a pre-malignant stage in progression to many cancers. However, field defects are often overlooked in studies of cancer progression through assuming tissue at some distance from the cancer is normal. We indicate, however, the generality of field defects in gastrointestinal cancers, including cancers of the oropharynx, esophagus, stomach, bile duct, pancreas, small intestine and colon/rectum. Common features of these field defects are reduced apoptosis competence, aberrant proliferation and genomic instability. These features are often associated with high bile acid exposure and may explain the association of dietary-related factors with cancer progression.

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Association of COX‐2 expression with corresponding active and chronic inflammatory reactions in Barrett's metaplasia and progression to cancer

Cited by 16 publications

References 35 publications

Met expression is an independent prognostic risk factor in patients with oesophageal adenocarcinoma

Met expression is an independent prognostic risk factor in patients with oesophageal adenocarcinoma

Evaluation of the immunoexpression of COX-1, COX-2 and p53 in Crohn's disease

Field defects in progression to gastrointestinal tract cancers

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