Association of Helicobacter pylori infection with atrophic gastritis and intestinal metaplasia

AIMS: To evaluate the effect of Helicobacter pylori infection and aging on atrophy and intestinal metaplasia of the gastric mucosa. METHODS: One hundred and sixty-three patients were divided into three age groups and underwent an upper gastrointestinal endoscopy where no esophagitis, peptic ulcers, or malignancies were detected. Two biopsy specimens were obtained from the anterior and posterior walls of the antrum and of the fundus. These were used to evaluate the grade of gastritis, bacterial culture and histologic evidence of H. pylori infection. RESULTS: Helicobacter pylori infection was found to be directly associated with an increased risk of gastritis grade (odds ratio (OR) = 90 (95% CI; 30-270)). An age of 60 years and older along with H. pylori infection was also strongly associated with an increased risk of atrophy (OR = 6.6, (95% CI; 2.9-15.2)); OR = 9.8, (95% CI; 2.7-35.4)), as was intestinal metaplasia of the gastric mucosa (OR = 5.5, (95% CI; 1.7-17.6)); OR = 7.9, (95% CI; 2.8-46.1)). The prevalence of atrophic gastritis increased with advancing age in H. pylori-infected patients, but no such phenomenon was observed in H. pylori-uninfected patients. The prevalence of intestinal metaplasia significantly increased with advancing age, irrespective of the presence of H. pylori infection. In addition, H. pylori uninfected female patients had a decreased risk of intestinal metaplasia. CONCLUSIONS: These results suggest that atrophic gastritis is not a normal aging process, but instead is likely to be the result of H. pylori infection, while intestinal metaplasia is caused by both the aging process and H. pylori infection. A decreased risk of intestinal metaplasia found in uninfected female subjects may partly explain the lower prevalence of gastric cancer in females than in males.     

Antral-type mucosa in the gastric incisura, body, and fundus (antralization): a link between Helicobacter pylori infection and intestinal metaplasia?

OBJECTIVES: Helicobacter pylori is a carcinogen; gastric carcinoma involves a multistep process from chronic gastritis to atrophy, intestinal metaplasia, and dysplasia. The aims of this study were to determine the types of mucosa at different gastric sites in H. pylori-infected and uninfected patients, and whether the presence of antral-type mucosa in the incisura, body, and fundus is associated with gastric atrophy and intestinal metaplasia. METHODS: Two hundred and sixty-eight patients with dyspepsia were enrolled. Eight biopsies (i.e., antrum x3, body x2, fundus x2, and incisura x1) were obtained. One antral biopsy was used for the CLO-test. Three (each from the antrum, body, and fundus) were cultured. The remaining biopsies were examined histologically according to the updated Sydney System after staining with hematoxylin and eosin and Giemsa. A validated serological test was also applied. RESULTS: Overall, 113 (42%) patients were infected with H. pylori. At the incisura, antral-type mucosa was more prevalent in infected than in uninfected patients (84% vs. 18%; odds ratio [OR] = 23.9, 95% confidence interval [CI] 12.5-45.8; p<0.001). Atrophic gastritis and intestinal metaplasia at the incisura was present in 19.5% and 13.3%, respectively, of infected, and 4.5% and 3.2%, respectively, of uninfected patients (both p<0.01). Moreover, atrophic gastritis at the incisura was associated with the presence of antral-type mucosa at the site (termed antralization); the prevalence of atrophic gastritis was 19.5% (24/123) in the presence of antralization, whereas the rate was 2.1% (3/145) without antralization (OR = 11.4, 95% CI 3.4-39.2; p<0.001). Similarly, at the incisura, 16.3% (20/123) of "antralized" cases and 1.4% (2/145) of "unantralized" cases had intestinal metaplasia (OR = 13.8, 95% CI, 3.2-60.7; p<0.001). The association between antralization at gastric body and fundus also appeared to be associated with atrophic gastritis and intestinal metaplasia at these sites. CONCLUSIONS: Atrophic gastritis and intestinal metaplasia occurs predominantly at the gastric antrum and incisura with H. pylori infection. Antralization of the gastric incisura is a common event in H. pylori-infected patients, and appears to be associated with an increased risk of atrophic gastritis and intestinal metaplasia.     

Long-term treatment with sterigmatocystin,a fungus toxin,enhances the development of intestinal metaplasia of gastric mucosa in Helicobacter pylori-infected Mongolian gerbils

BACKGROUND: Helicobacter pylori is a human gastric carcinogen. Sterigmatocystin (ST), a fungus toxin, is a risk factor of gastric cancer. Cytotoxin-vacuolation toxin A (VacA) present in supernatants of H. pylori suspensions can cause gastritis and ulcer. The aim of this study was to examine the effects of H. pylori, ST and VacA in Mongolian gerbils. METHODS: Male Mongolian gerbils (n = 196) were treated with H. pylori supernatants (10 ml/1000 mg) mixed with diet or inoculated intragastrically with H. pylori alone or with ST (100 or 1000 ppb), and then killed 27 months later. Gastric tissue sections were stained with haematoxylin and eosin (H&E), periodic acid-Schiff (PAS), Alcian blue (AB, pH 2.5) and with immunostaining for PCNA and p53 expression. RESULTS: In H. pylori-infected gerbils, the normal mucosa was replaced by hyperplastic epithelium. Severe gastritis, cystic dilatation of gastric glands, hyperplastic polyps and intestinal metaplasia were observed. In H. pylori + ST (1000 ppb) gerbils, intestinal metaplasia was significantly more frequent than in H. pylori alone animals. No pathological changes were observed in the H. pylori supernatant group. Osseous metaplasia was observed in the H. pylori + ST (100 ppb) group. Serum gastrin levels of the H. pylori + ST (1000 ppb) group were significantly higher than those of the other groups. PCNA labelling index and p53 index of infected gerbils were significantly higher than those of uninfected groups. CONCLUSION: H. pylori causes gastritis, ulcer and intestinal metaplasia. ST enhances the development of intestinal metaplasia and increases gastrin levels in H. pylori-infected Mongolian gerbils.     

Role of N-methyl-N-nitrosourea in the induction of intestinal metaplasia and gastric adenocarcinoma in Mongolian gerbils infected with Helicobacter pylori

BACKGROUND: Progression from intestinal metaplasia to neoplasia has not been demonstrated experimentally. The hypothesis that gastric adenocarcinoma arises from intestinal metaplasia was tested in a Mongolian gerbil model of Helicobacter pylori (H. pylori) infection. METHODS: One hundred and fourteen specific pathogen-free gerbils were divided in five groups. A and D: infected with H. pylori and administered the carcinogen N-methyl-N-nitrosourea (MNU); C and E: received MNU; B: H. pylori, but no MNU. Animals were killed at 41 weeks, stomachs were mapped, and the relationship between metaplasia and cancer was assessed. RESULTS: Intestinal metaplasia occurred more frequently in the H. pylori-infected, MNU-treated gerbils than in those receiving H. pylori inoculation only (P < 0.01). Carcinomas arose only in H. pylori-infected animals receiving MNU (8 well differentiated, 2 poorly differentiated, and 10 signet ring). Intestinal metaplasia occurred more frequently in association with intestinal-type carcinoma. CONCLUSIONS: Intestinal metaplasia and adenocarcinoma arise in stomachs subjected to the same injuries (in this study, H. pylori and MNU). Only two intestinal-type carcinomas were contiguous to intestinal metaplasia; all other tumors developed most commonly at non-metaplastic sites. This suggests that in this animal model H. pylori and MNU induce several phenotypes of gastric cancer, but intestinal metaplasia may be a direct precursor only in a subset of the intestinal-type tumors.     

Frequent and rapid progression of atrophy and intestinal metaplasia in gastric mucosa of patients with MALT lymphoma

OBJECTIVES: Association of gastric mucosa-associated lymphoid tissue (MALT) low-grade lymphoma and adenocarcinoma has repeatedly been reported. The aim of this study was to evaluate the frequency and the spreading of atrophy and intestinal metaplasia in gastric mucosa of patients with gastric MALT lymphoma followed after conservative treatment. METHODS: Forty-five patients (mean age 45 +/- 2.1 yr) with gastric MALT lymphoma, treated by Helicobacter pylori eradication, chemotherapy with per os single alkylating agents, or both treatments have been followed by gastroscopy with biopsies in antrum and corpus at least once a year. Univariate and multivariate analysis evaluated the association between the appearance of atrophy and intestinal metaplasia in antrum or corpus and different factors related to patients, H. pylori status, lymphoma features, and treatment. In addition, histological aspects of gastric biopsies at the diagnosis period and at the end of follow-up were compared with those of two control groups of age-matched patients with H. pylori gastritis. RESULTS: At the diagnosis time, only intestinal metaplasia in corpus was more frequent in patients with gastric MALT lymphoma than in patients with nonulcer dyspepsia. Within median follow-up of 54.4 months (range 9-196), the percentage of patients with gastric atrophy and intestinal metaplasia increased significantly and became significantly higher than in age-matched nonulcer dyspepsia patients. Multivariate analysis showed significant association between corpus intestinal metaplasia and corpus atrophy, intestinal metaplasia in antrum, and duration of the follow-up. CONCLUSIONS: Conservative management of gastric MALT lymphoma including H. pylori eradication is associated with progression of gastric atrophy and intestinal metaplasia with frequent involvement of the corpus which is known to be a precancerous condition. These findings show that long-term endoscopic monitoring should be recommended in such patients.     

Helicobacter pylori infection and precancerous lesions of the stomach

H. pylori infection is associated with a slightly increased risk of gastric cancer. However, the risk is much higher in the subgroup of infected patients who have atrophic gastritis and extensive intestinal metaplasia. In those subjects, H. pylori acts as a trigger of the sequence which begins as atrophic gastritis with intestinal metaplasia and evolves towards immature forms of intestinal metaplasia and dysplasia. It seems that factors different from H. pylori (diet, genetical background, etc.) might have an influence on how often gastric precancerous lesions appear in H. pylori-infected subjects. Effective prevention of gastric carcinoma would require identification of the patients at risk in an early step of the process. Preventive measures would include H. pylori eradication and changes in the diet (i.e., increase of vitamin C and carotenoid intake). Preliminary data suggest that H. pylori eradication cannot revert intestinal metaplasia. However, it is possible that eradication of the bacteria would prevent progression towards immature forms of intestinal metaplasia and dysplasia.     

Close correlation of intestinal metaplasia and corpus gastritis in patients infected with Helicobacter pylori

BACKGROUND: The role of intestinal metaplasia as a precancerous condition for Helicobacter pylori associated gastric carcinoma has been the subject of numerous investigations. The aim of the present study was to investigate whether other diffuse gastritis markers such as H. pylori gastritis in the corpus correlate with the presence of intestinal metaplasia and gastric carcinoma. METHODS: The histological records of 2,000 patients with H. pylori gastritis were retrospectively investigated for grade/activity of gastritis, and presence of intestinal metaplasia. RESULTS: There was a strong correlation between the degree and activity of H. pylori gastritis in the corpus and the presence of intestinal metaplasia in antrum or corpus (all P < 0.001). Intestinal metaplasia and pronounced corpus gastritis were found predominately in H. pylori infected persons with gastric cancer or benign gastric ulcers. CONCLUSIONS: On the basis of its close correlation with intestinal metaplasia, pronounced corpus gastritis may be considered as a marker of gastric cancer. In comparison with intestinal metaplasia, this marker of gastric cancer risk has the advantage of being associated with less interobserver variation, and - due to its diffuse presentation - a lower risk of sampling bias.     

Comparative classification and grading of Helicobacter pylori gastritis in patients with gastric cancer and patients with functional dyspepsia

BACKGROUND: It has previously been shown that corpus-dominant grade and activity of Helicobacter pylori gastritis in combination with intestinal metaplasia in the antrum or corpus are risk markers for the development of stomach cancer. If one point is scored for each of these three parameters, a gastric cancer risk index is obtained that permits prediction of the risk of gastric cancer developing on the soil of H. pylori gastritis. The aim of the present study was to evaluate the accuracy of the gastric cancer risk index based on a large number of patients compared with dyspeptic controls. METHODS: In 415 biopsied patients with gastric carcinoma, biopsy specimens taken from the antrum and corpus were investigated retrospectively. From this group of patients, 244 patients positive for H. pylori were compared with 244 sex- and age-matched H. pylori-infected patients with functional dyspepsia. RESULTS: H. pylori gastritis was detected in 395 carcinoma patients (95.2%). The 244 sex- and age-matched patients significantly more frequently had corpus-dominant H. pylori gastritis (compared with NUD controls). The incidence of intestinal metaplasia was also significantly increased. For a gastric cancer risk index score of 3 points (i.e. corpus pronounced grade and activity of gastritis, and intestinal metaplasia in antrum or corpus), a sensitivity of 93% and a specificity of 85% for the presence of gastric carcinoma can be calculated. CONCLUSION: Using the proposed risk index, the topographic grading of H. pylori gastritis in the antrum and corpus enables the diagnosis of a 'risk gastritis' to be made.     

A functional promotor polymorphism of TNF-alpha is associated with primary gastric B-Cell lymphoma

BACKGROUND AND AIMS: The host genetic background to develop primary gastric B-cell lymphoma in patients with chronic Helicobacter pylori infection is unknown. Tumor necrosis factor (TNF)-alpha plays a key role in H. pylori-associated inflammation and appears to be involved in the evolution of lymphoproliferative disorders. We investigated four functional promotor polymorphisms in the TNF-alpha gene for association with the development of primary gastric B-cell lymphoma. PATIENTS AND METHODS: A total of 144 lymphoma patients, 595 H. pylori-infected controls and 534 healthy blood donors were genotyped for TNF-alpha-238, -308, -857, and -1031 by Taqman technology and case-control analysis was conducted. RESULTS: There was no significant difference in allele and genotype frequencies in H. pylori-infected patients and healthy controls. TNF-857 T allele was found in 15.1% of patients with low-grade lymphoma and 9.1% of H. pylori-infected patients (Pearson's=5.7, p=0.017, OR=1.8, Wald 95% CI: 1.1< O.R.< 2.8). Carrier of the rare allele T had a 1.8-fold increased risk to develop low-grade lymphoma (Pearson's=5.4, p=0.021). Patients with high-grade lymphoma were significantly more frequent carriers of the TNF-857 T allele than healthy blood donors (30.9%vs 18.9%, Pearson's=4.5, p=0.033). Carriage of the T allele conferred a 1.9-fold increased risk (Wald 95% CI: 1.0相似文献   

p27kip1 deficiency confers susceptibility to gastric carcinogenesis in Helicobacter pylori-infected mice

BACKGROUND & AIMS: Determining how Helicobacter pylori promotes gastric cancer and whether H pylori eradication decreases cancer risk would be helped by suitable murine models. Mice lacking the cyclin-dependent kinase inhibitor p27kip1 are susceptible to carcinogen-induced tumors. Furthermore, p27 stimulates gastric epithelial apoptosis and inhibits proliferation, expression is decreased by H pylori, and low levels are associated with a poor prognosis in gastric cancer. We therefore evaluated p27-deficient mice as a model for H pylori-associated gastric cancer. METHODS: Wild-type and p27-/- C57BL/6 mice were infected with H pylori mouse-adapted Sydney strain at 6-8 weeks of age and 6-10 mice of each type were euthanized 15, 30, 45, 60, and 75 weeks later. RESULTS: Uninfected p27-/- mice developed gastric hyperplasia. H pylori-infected p27-/- mice frequently developed intestinal metaplasia (40% at 30 weeks, 67% at 45 weeks), and after 60 weeks 7 of 12 mice developed significant dysplasia and gastric cancer, recapitulating human intestinal-type gastric carcinogenesis. Wild-type mice developed intestinal metaplasia only after 75 weeks of infection; significant gastric dysplasia was observed in 1 animal (P < .05 for each comparison with p27-/- mice). No disease developed in uninfected mice. H pylori infection in p27-/- mice was associated with significantly decreased apoptosis and increased epithelial proliferation, inflammation, and H pylori density compared with infection in wild-type mice. CONCLUSIONS: p27 loss and H pylori colonization cooperate to produce gastric cancer. The p27-deficient mouse affords opportunities to examine the pathogenesis of H pylori in gastric carcinogenesis and to test eradication and chemopreventive strategies.     

ABH and Lewis antigen distributions in blood, saliva and gastric mucosa and H pylori infection in gastric ulcer patients

AIM:To investigate the ABH and Lewis antigen expres-sion in erythrocytes,saliva and gastric epithelium,aswell as the association between H pylori and the pres-ence of gastric epithelial lesions.METHODS:The distribution of ABH and Lewis bloodgroup antigens in erythrocytes,saliva and gastric mu-cosa of H pylori-infected gastric ulcer patients was ana-lyzed.Forty-two patients with gastric ulcer were studied,and fifty healthy individuals were used as control group.The blood group antigens were determined by directhemagglutination,dot-ELISA and immunohistochemi-cal methods in erythrocytes,saliva and gastric mucosaspecimens,respectively.Diagnosis for H pylori infectionwas performed by conventional optical microscopy andELISA.RESULTS:A higher seroprevalence of IgG H pylori spe-cific antibodies was observed in gastric ulcer patients(90%)compared to the control group(60%).We ob-served a significant increase of phenotypes O,A_2 andLewis b in H pylori-infected patients.The expression ofthese antigens had progressive alterations in areas of ul-cerous lesions and intestinal metaplasia. CONCLUSION:ABH and Lewis blood group antigensare a good indicator for cellular alterations in the gastricepithelium.     

Helicobacter pylori infection as a risk factor for gastric ulceration

BACKGROUND/AIMS: Recent reports have shown that Helicobacter pylori infection is closely related to pathogenesis of gastric ulcers. But there have been no reports on the prospective follow-up study of the patients with H. pylori infection to determine whether H. pylori infection puts patients at high risk of developing gastric ulcers. METHODOLOGY: Fifty-two patients with H. pylori infection and 34 patients without H. pylori infection, who were found endoscopically not to have localized lesions in the esophagus, stomach, or duodenum, underwent endoscopy follow-ups during the average observation period of 52 months. During each endoscopy, biopsy specimens were obtained from the antrum and the middle corpus. The grade of atrophy and intestinal metaplasia in the biopsy specimens were assessed histologically in accordance with the guidelines of the Updated Sydney System. RESULTS: Gastric ulcers developed in 8 (15%) of 52 patients with H. pylori infection, but not in patients without H. pylori infection: the difference was statistically significant (P<0.05). The development and the location of gastric ulcers was correlated to the development or progression of mucosal atrophy. In 8 (38%) of 21 patients in whom mucosal atrophy developed or progressed, gastric ulcers developed, but no ulcers developed in 31 patients without development or progression of gastric mucosal atrophy. Gastric ulcers developed in the gastric mucosa in which atrophy developed or progressed. CONCLUSIONS: H. pylori infection increases the risk for development of gastric ulcers and gastric ulcers developed through the progression of H. pylori-associated gastric mucosal atrophy.     

Effect of Helicobacter pylori infection on Bax protein expression in patients with gastric precancerous lesions

AIM: To investigate the effect of Helicobacter pylori (H pylori) infection on Bax protein expression, and explore the role of H pylori in gastric carcinogenesis. METHODS: H pylori was assessed by rapid urease test and Warthin-Starry method, and expression of Bax protein was examined immunohistochemically in 72 patients with pre-malignant lesions. RESULTS: Bax protein was differently expressed in intestinal metaplasia and gastric dysplasia, and showed 63.99% positivity. The positivity of Bax protein expression in Hpylori-positive gastric precancerous lesions (72.3%) was significantly higher than that in H pylori-negative gastric precancerous lesions (48.0%, X~2=4.191, P<0.05). H pylori infection was well correlated with the expression of Bax protein in gastric precancerous lesions (r=0.978, P<0.01). After eradication of H pylori, the positivity of Bax protein expression significantly decreased in H pylort-positive gastric precancerous lesions (X~2=5.506, P<0.05). In the persisting H pylori-infected patients, the positivity of Bax protein expression was not changed. CONCLUSION: H pylori infection may be involved in the upregulation of Bax gene, which might be one of the mechanisms of H pylori infection-induced gastric epithelial cell apoptosis. H pylori might act as a tumor promoter in the genesis of gastric carcinoma and eradication of H pylori could inhibit gastric carcinogenesis.     

Subtypes of intestinal metaplasia and Helicobacter pylori.

To determine whether there is a relationship between the presence of H pylori and the various subtypes of intestinal metaplasia in the gastric antrum, 2274 antral gastroscopic biopsies from 533 patients were examined. H pylori was found in 289 patients. Intestinal metaplasia in general was found in 135 patients. Type I intestinal metaplasia was found in 133 patients (98.5%), type II in 106 patients (78.5%) and type III in 21 patients (15.6%). Ninety eight of these 135 patients (72.6%) were H pylori positive and 37 patients (27.4%) were H pylori negative. No statistically significant difference was found in the prevalence of type I and II intestinal metaplasia between the intestinal metaplasia positive and H pylori positive and intestinal metaplasia negative and H pylori negative patients. Type III intestinal metaplasia was found less often in the intestinal metaplasia positive and H pylori positive patients (11.2%) as compared with intestinal metaplasia positive and H pylori negative patients (27%) (p less than 0.05). In contrast with type I and II intestinal metaplasia type III intestinal metaplasia was found more often in moderate/severe intestinal metaplasia than in mild intestinal metaplasia (p less than 0.02). Within the group of patients with moderate/severe intestinal metaplasia, type III was found less often in the H pylori positive patients (p less than 0.05). We suggest that the gastric milieu for H pylori is less appropriate in type III intestinal metaplasia positive patients. As type III intestinal metaplasia might be regarded as a marker of possibly increased gastric cancer risk, the lower prevalence of H pylori in these type III intestinal metaplasia positive patients might be the result of severe changes in mucosal architecture.     

Host TNF-alpha-1031 and -863 promoter single nucleotide polymorphisms determine the risk of benign ulceration after H. pylori infection

OBJECTIVES: This study tested whether host genotypes of the tumor necrosis factor-alpha (TNF-alpha) promoter single nucleotide polymorphism (SNP) could determine clinical and histological outcomes after Helicobacter pylori infection. METHODS: A total of 524 dyspeptic patients, 424 with and 100 without H. pylori infection, were checked for TNF-alpha promoter SNP over the locus on -1031(T/C), -863(C/A), -857(C/T), -806(C/T), and -308(G/A) by sequence-specific oligonucleotide probe. Each patient received panendoscopy to take gastric biopsy to detect H. pylori infection and its related histology using the updated Sydney's system. Gastric TNF-alpha expressions were stained by immunohistochemistry. RESULTS: In H. pylori-infected patients, -1031C or -863A carriers of TNF-alpha promoter had more severe gastric neutrophil infiltration and TNF-alpha gastric staining than individuals with -1031TT or -863CC genotype, respectively (p<0.05). The multivariate logistic regression verified both -1031C and -863A carriers were independent risk factors to have duodenal ulcers and gastric ulcer without IM in the H. pylori-infected hosts (p<0.05). As compared to -863CC and -1031TT genotype combinations, the ulcer risk after H. pylori infection was 2.46 (95% CI: 1.32-4.59, p相似文献   

Improvement of gastric atrophy after Helicobacter pylori eradication therapy

BACKGROUND: It remains controversial whether gastric atrophy is reversible after Helicobacter pylori eradication therapy. AIM: To clarify whether gastric atrophy improves after H. pylori eradication therapy using a histologic approach. METHODS: Subjects were 87 H. pylori infection-cured patients (treatment group) and 29 continuously H. pylori-infected patients (control group). The subjects in the treatment and control groups were followed for 10-49 months (mean, 22 months) and 11-50 months (mean, 22 months), respectively. Biopsy specimens were obtained from the greater curvature of the antrum and corpus at the beginning and end of the observation period; histologic analyses of these specimens were performed for detection of activity, inflammation, atrophy, and intestinal metaplasia. Results were scored without any clinical information according to the Sydney system. RESULTS: In the treatment group, the histologic score for atrophy was improved in the corpus but not in the antrum. Intestinal metaplasia was not improved in either the antrum or the corpus. There were no significant differences during the follow-up in gastric atrophy and intestinal metaplasia in the control group. CONCLUSION: Gastric atrophy was improved in the corpus approximately 2 years after H. pylori eradication therapy.     

Cell kinetic balance in gastric mucosa with intestinal metaplasia after Helicobacter pylori eradication: 2-year follow-up study

BACKGROUND: Proliferation and apoptosis events are altered in Helicobacter pylori infection. However, whether H. pylori eradication has an effect on the disturbed kinetics in metaplastic mucosa has not been well elucidated. AIM: To investigate the effect of eradication on the gastric cell kinetics. SUBJECTS AND METHODS: Initially, biopsies were obtained from 74 H. pylori-infected subjects and repeated 12 and 24 months after eradication. Biopsies were immunohistochemically stained for apoptosis by single-stranded DNA, for proliferation by Ki-67 antibodies and for intestinal metaplasia MUC2, MUC5AC, MUC6 and CD10. RESULTS: While antral apoptosis in intestinal metaplasia was significantly lower than in non-intestinal metaplasia, proliferation was significantly higher (greater and lesser curvatures, P < 0.05, respectively). This resulted in a significantly lower apoptosis/proliferation ratio in intestinal metaplasia than in non-intestinal metaplasia (antrum greater and lesser curvatures and corpus greater curvature, P < 0.05). After successful eradication, apoptosis and proliferation decreased in both intestinal metaplasia and non-intestinal metaplasia. The pattern of reduction of apoptosis and proliferation differed in these two groups. However, in the corpus, the reduction resulted in a significant increase in the apoptosis/proliferation ratio in both. CONCLUSION: Proliferation and apoptosis are unevenly and disproportionately altered in H. pylori infection leading to an imbalance in cell kinetics. Eradication of the organism improves the balance and may possibly play a role in the prevention of malignancy transformation in the metaplastic mucosa.     

HLA-DQB1 locus and gastric cancer in Helicobacter pylori infection

BACKGROUND AND AIMS: It has been suggested that the incidence of digestive diseases associated with Helicobacter pylori is influenced by the strain diversity of H. pylori, factors involving the host or environment, and the duration of infection. The authors have previously reported that human leukocyte antigen (HLA)-DQB1*0401 plays an important role in the development of atrophic gastritis in H. pylori infected patients. The aim of the present study was to investigate the relationship between HLA-DQB1 genotype and cancer development. METHODS: HLA-DQB1 genotyping was performed by the PCR-RFLP method on 122 H. pylori-infected non-ulcer dyspepsia (NUD) patients, 53 gastric cancer patients and 28 uninfected controls. To reliably estimate the grade of atrophic gastritis, histological evaluation was performed. RESULTS: The allele frequency of DQB1*0401 was significantly higher in intestinal type cancer patients compared with age- and sex-matched H. pylori-infected NUD patients. There was no significant difference in the mean atrophic scores of the biopsy samples from the lesser curvature of the mid-corpus between these groups. CONCLUSIONS: HLA-DQB1*0401 is a useful marker for determining susceptibility to intestinal type gastric cancer.