Preferential expression of cyclooxygenase-2 in colonic-phenotype of gastric intestinal metaplasia: association with helicobacter pylori and gastric carcinoma.
ABSTRACT Gastric intestinal metaplasia (GIM) associated with H. pylori (HP) has been considered a premalignant lesion. However, GIM phenotype associated with HP infection and gastric cancer is unclear. The expression of COX-2 in relation to GIM phenotype is also unknown.
We evaluated cellular phenotype and COX-2 expression in the GIM from HP-positive and -negative patients from Japan in the absence of gastric cancer (n = 31) by using a colon epithelium specific monoclonal antibody (mAb Das-1) and anti-COX-2 antibody. COX-2 expression was also examined in patients with gastric cancer (n = 34), both in the cancer and in the GIM areas away from the cancer field.
Sixty-eight percent of HP-positive GIM reacted with mAb Das-1, whereas the reactivity in the HP-negative GIM was only 25% (P < 0.001). The COX-2 expression was present in 32% of HP-positive GIM and in only 9% of HP-negative GIM (P < 0.001). In the cancer group, COX-2 expression was localized both in the cancer area (94%) and in the GIM (82%) away from the cancer. Each of the COX-2-positive tissue was also positive to mAb Das-1.
HP infection is highly associated with the development of colonic-phenotype of GIM, and about half of them expressed COX-2. COX-2 expression was frequent in both gastric cancer and the GIM adjacent to the cancer. The results suggest that the presence of mAb Das-1 and COX-2 reactivity in the GIM identify the subgroup of patients who may be at risk for gastric cancer and may need close surveillance.
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ABSTRACT: Small amounts of PGE inhibit mitogen-induced [3H]thymidine incorporation in human peripheral lymphocytes. The 50% inhibitory concentration is approximately 10(-7) M, and this is reduced to approximately 10(-8) M when endogenous PGE production is blocked. PGE inhibits PHA- and Con A-stimulated cultures much better than PWM cultures, suggesting a differential effect of PGE on T-cell vs. B-cell function. In vitro blockade of PG synthesis results in approximately 50% increase in [3H]thymidine incorporation in PHA cultures. PGE is produced endogenously in PHA cultures by glass adherent suppressor cells.Journal of Experimental Medicine 01/1978; 146(6):1719-34. · 13.21 Impact Factor
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ABSTRACT: Between 1967 and 1976, 1,525 Slovenian patients with a histological diagnosis of intestinal metaplasia (IM) were classified according to subtype of IM based on morphology and mucin staining; 518 cases were diagnosed with type I, 197 with type II and 275 with type III, but in 291 the diagnosis of IM was not confirmed. Patients who had developed cancer or died up to 1986 were identified by record linkage at the Slovenia Cancer Registry and the Central Population Registry in Slovenia. A total of 34 incident cases of gastric cancer occurring at least 6 months after the diagnosis of IM were identified. The standardised incidence ratio (SIR) for stomach cancer was 2.23 in the whole cohort. It was highest for IM type III, followed by type II and IM-unconfirmed, but not increased for type I. The relative risk (RR) of developing gastric cancer based on Cox's proportional hazards model was 2.14 for type II and 4.58 for type III, compared with type I. The RR was especially increased for a subgroup of type III secreting sulphomucins in their goblet cells in comparison with types I-II negative to sulphomucins. Our results confirm that subtyping of IM is useful for identifying individuals at high risk for gastric cancer.International Journal of Cancer 06/1994; 57(3):324-9. · 6.20 Impact Factor
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ABSTRACT: Within the framework of a chemoprevention trial on stomach cancer, two substudies based on repeat measurement were undertaken to evaluate reliability of histological diagnoses of gastric precancerous lesions. A subgroup of 45 subjects received two endoscopies separated by a period of one month. The two biopsies were reviewed by a single pathologist. A second subsample of 50 subjects had a single endoscopy and the biopsy results were reviewed by two pathologists. Agreement between the two diagnoses was assessed by Cohen's Kappa and by repeat frequency. When the same samples were reviewed by the pathologists involved in the trial, agreement was very high for advanced lesions (repeat frequency = 0.96 for intestinal metaplasia and 1.00 for dysplasia) but lower for less advanced lesions (repeat frequency = 0.73 for superficial gastritis and chronic gastritis, 0.65 for atrophic gastritis). When the same pathologist reviewed two sets of biopsies taken less than 2 months apart, the combination of random observer error and biopsy sampling error gave rise to quite low agreement, especially for early lesions, mainly attributable to biopsy sampling error. Comparison of diagnoses made at routine reading and at review by the same pathologist and by different pathologists showed substantial overall agreement with the exception of one pathologist for whom agreement was moderate. These results confirm that misclassification of histological diagnosis may be a relevant problem in chemoprevention trials of stomach cancer, more so when baseline diagnosis is taken into account in the analysis to estimate progression and regression rates of precancerous lesions. Further, the results suggest that misclassification is limited to early lesions, while diagnostic reliability of severe lesions is quite high.International Journal of Epidemiology 09/1997; 26(4):716-20. · 6.98 Impact Factor