Ana Margarida Miguel Ferreira Nogueira

Gastric carcinoma exhibits distinct types of cell differentiation: an immunohistochemical study of trefoil peptides (TFF1 and TFF2) and mucins (MUC1, MUC2, MUC5AC, and MUC6).

The expression of trefoil peptides (TFF1 and TFF2) and mucins (MUC1, MUC2, MUC5AC, and MUC6) has previously been described in gastric polyps. In the present study, the expression profile of these trefoil peptides and mucins was characterized in 96 gastric carcinomas, in an attempt to further the understanding of the histogenesis and cell differentiation of gastric carcinoma. Taking together the co‐expression of trefoil peptides and mucins, three phenotypes were defined: complete gastric, incomplete gastric, and non‐gastric phenotype. Gastric differentiation (complete and incomplete) was observed in 30 out of 33 (90.9%) diffuse carcinomas and in 38 out of 53 (71.7%) intestinal carcinomas. Non‐gastric differentiation was observed in only three (9.1%) diffuse carcinomas and in 15 (28.3%) intestinal carcinomas. The phenotypes observed in intestinal carcinomas were similar to those previously observed in adenomatous polyps, whereas most diffuse carcinomas mimicked the phenotype of hyperplastic polyps. The percentage of cases displaying a non‐gastric phenotype was higher, though not significantly, in tumours that had invaded the gastric wall than in T1 tumours, regardless of histotype. It is concluded that gastric‐type differentiation is retained in the majority of gastric carcinomas, being more prominent in diffuse than in intestinal carcinomas, and in early than in advanced carcinomas. Copyright

Evaluation of [13C]urea breath test and Helicobacter pylori stool antigen test for diagnosis of H. pylori infection in children from a developing country.

ABSTRACT The [13C]urea breath test (13C-UBT) and Helicobacter pylori stool antigen test (HpSA) for the diagnosis of H. pylori infection in children were validated. The sensitivity, specificity, and positive and negative predictive values were 93.8, 99.1, 97.8, and 98.0%, respectively, for the 13C-UBT and 96.9, 100, 100, and 98.0%, respectively, for HpSA. Both tests are appropriate for diagnosing H. pylori infection in children.

babA2- and cagA-positive Helicobacter pylori strains are associated with duodenal ulcer and gastric carcinoma in Brazil.

ABSTRACT The babA2 and cagA genes were investigated in 208 Brazilian Helicobacter pylori strains. A strong association between babA2 and duodenal ulcer or gastric carcinoma was observed, even after adjusting for confounding factors, such as age, gender, and cagA status. cagA-positive strains were also independently associated with H. pylori-related diseases.

New Pathogenicity Marker Found in the Plasticity Region of the Helicobacter pylori Genome

ABSTRACT Comparison of gastric carcinoma and gastritis isolates showed the presence of genes, probably carcinoma associated (JHP947 and JHP940), that are situated in a Helicobacter pylori genome region (45 kb in J99 and 68 kb in 26695) called the “plasticity region.” This region presents a great variability of DNA sequences. We investigated, by PCR, the presence of the JHP940 and JHP947 genes, as well as the presence of a third gene which seems to be associated with gastritis (HP986), on H. pylori strains isolated from 200 Brazilian patients, 79 of whom had gastric carcinomas and 53 of whom had duodenal ulcers, to confirm this association. Gastritis isolates (n = 68) were included as a control. We also evaluated if these genes were related to the virulence-associated cagA genotype. The present methodology did not permit definitive conclusions to be reached regarding the association between the JHP940 gene and gastric carcinoma or between the HP986 gene and gastritis. However, we showed that the JHP947 gene might be implicated in the development of both duodenal ulcer and gastric carcinoma. The presence of the JHP947 gene was associated with the cagA-positive genotype. The JHP947 gene is a novel virulence marker candidate of H. pylori.

Patterns of expression of trefoil peptides and mucins in gastric polyps with and without malignant transformation

The expression of two trefoil peptides (TFF1 and TFF2) and four mucins (MUC1, MUC2, MUC5AC, and MUC6) was evaluated by immunohistochemistry and reverse transcription‐polymerase chain reaction (RT‐PCR) in 29 gastric polyps, 10 hyperplastic and 19 adenomatous, eight of which displayed malignant transformation. The aims of this study were to characterize the expression profile of these molecules in each type of polyp and to investigate possible modifications of the profile during the process of malignant transformation. All hyperplastic polyps displayed immunoreactivity for TFF1, MUC5AC, and MUC1 in more than 75 per cent of the cells. In adenomatous polyps, three main phenotypes could be identified: complete gastric phenotype (co‐expression of TFF1 and MUC5AC)—nine cases (47·4 per cent); incomplete gastric phenotype (TFF1‐positive and MUC5AC‐negative)—seven cases (36·8 per cent); non‐gastric (intestinal) phenotype (no expression of TFF1 or MUC5AC)—three cases (15·8 per cent). Data yielded by immunohistochemistry and RT‐PCR showed a good correlation for both TFF1 and TFF2. One hyperplastic and seven adenomatous polyps with villous architecture displayed foci of diffuse and intestinal‐type carcinoma, respectively; in all of these cases, MUC1 expression and signs of gastric differentiation were observed in both the non‐malignant and the carcinomatous component. It is concluded that gastric differentiation is a feature of hyperplastic polyps and of a subset of adenomatous polyps which is shared by early carcinomas arising in some of these polyps, regardless of the histological type of polyp and of carcinoma. Copyright

iceA Genotypes of Helicobacter pylori Strains Isolated from Brazilian Children and Adults

ABSTRACT Data concerning the geographic distribution of iceAalleles are scarce, and information on the association of the gene with the disease is rare and still controversial. Furthermore, no such study has been developed in Brazil, where duodenal ulcer and gastric adenocarcinoma are very common. We investigated, by PCR, the frequency of iceA alleles and cagA status inHelicobacter pylori strains isolated from 142 patients (62 children and 80 adults; 66 female; mean age, 30.0 years; age range, 3 to 78 years) with gastritis, duodenal ulcer, or gastric adenocarcinoma.iceA was identified in bacterium samples obtained from all patients. Eleven (7.7%) of them were infected with multiple strains. Among the patients with nonmixed infection, iceA2 allele was detected in 118 (90.1%). iceA2 allele was associated with ulcer (P = 0.02) and with carcinoma (P = 0.001). iceA2 amplicons of 229, 334, or 549 bp were detected, but none of them was associated with the patients disorder. iceA2 strains were more frequent in patients older than 7 years (P = 0.001). The gene was also more frequent in strains obtained from males (P = 0.02). cagA was more common in strains obtained from carcinoma (P = 0.0008) and ulcer patients (P < 0.006). cagA-positive strains were more frequent in children older than 7 years (P < 0.003). No association between cagA status and sex was found (P = 0.28). In conclusion, we thinkiceA should not be used as a reliable marker for predicting the clinical outcome of H. pylori infection.

Promoter methylation of TGFβ receptor I and mutation of TGFβ receptor II are frequent events in MSI sporadic gastric carcinomas

Transforming growth factor beta (TGFβ) is a potent inhibitor of cell growth, whose action is transduced through interaction between type I (RI) and type II (RII) receptors. Abnormal expression of these receptors has been identified in several human cancers and was found to be associated with resistance to TGFβ. TGFβ RII mutations occur in many types of malignancy. TGFβ RI hypermethylation has been suggested as a cause of abnormal or absent expression of this receptor in cancer. This study has analysed the methylation status of the promoter region of the TGFβ RI gene using a methylation‐sensitive enzyme followed by polymerase chain reaction (PCR), and TGFβ RII mutations (BAT‐RII and a GT3) in order to determine the frequency of alteration of the TGFβ receptors in a series of 40 sporadic gastric carcinomas (SGCs), 25 of which showed microsatellite instability (MSI) and 15 of which were microsatellite stable (MSS). Methylation in the promoter region of the TGFβ RI gene was detected in 20 of the 40 (50%) SGCs (64% of the MSI cases and 26.7% of the MSS); 17 of the 40 (42.5%) cases had mutations in the BAT‐RII region of the TGFβ RII gene (68% in the MSI cases; 0% in the MSS). In total, 25 of the 40 (62.5%) SGCs had alterations in at least one of the TGFβ receptors (84% of the cases in the MSI group, in contrast with 16% of the MSS cases) (p = 0.0003). The clinicopathological features of the cases were also studied and significant associations were found between the presence of alterations in TGFβ receptors and the age of the patients (p = 0.046), size (p = 0.011), and proliferative rate of the tumours (p = 0.048). In conclusion, alterations in the receptors of TGFβ (TGFβ RI promoter hypermethylation and TGFβ RII mutations) are frequent events in MSI SGC and are associated with large size and high proliferative activity of the tumours, in keeping with loss of the growth inhibitory effects of TGFβ in this setting. Copyright

Factors Associated with Helicobacter pylori Infection by a cagA-Positive Strain in Children

Although infection with a cagA-positive Helicobacter pylori strain is considered a risk factor for the development of duodenal peptic ulcer in adults, this association has not been demonstrated in children. The presence of cagA was investigated by polymerase chain reaction in H. pylori strains isolated from 27 children with duodenal ulcer and 53 without duodenal ulcer. All patients (100%) with duodenal ulcer and 33 (62.3%) without ulcer were colonized by a cagA-positive strain (P=.00007). A cagA-positive status was also associated with a more marked macroscopic gastritis, with a greater inflammatory infiltrate of both mononuclear and polymorphonuclear cells in the antral and oxyntic gastric mucosae and degenerative and regenerative changes of the gastric mucosa. Increased cagA positivity was also associated with increased age, but no association between cagA-positive status and sex was observed.

Spiral bacterium associated with gastric, ileal and caecal mucosa of mice

A spiral shaped bacterium was seen in smears and histological sections (stained by carbolfuchsin) of gastric, ileal and caecal mucosa as well as in stool smears from mice. A significant correlation between the presence of the spiral bacterium and the occurrence of gastritis was observed but the ileal and caecal mucosa seemed unaffected. The bacterium was Gram negative and grew on BHM and Skirrows medium, under microaerophilic conditions, at 37°C. Its major biochemical characteristics included positive catalase and oxidase reactions and a rapidly positive urease test. There were 2 or 3 spiral turns per cell and a tuft of up to 12 sheathed flagella on each pointed end. Entwined, braided periplasmic fibrils covered the surface of the cell. This spiral bacterium seemed to be part of the normal intestinal flora but was associated with gastritis.

Microsatellite Instability in Hyperplastic and Adenomatous Polyps of the Stomach

Few studies have focused on the presence and significance of microsatellite instability (MSI) in gastric polyps, and the results on record are conflicting. The aim of the current study was to address this issue, taking into consideration the 2 main types of gastric polyps, the coexistence of foci of malignant transformation, and the expression of p53 and ERBB‐2.