Fcγ-RI, Fcγ-RII and IL-10 as predictive biomarkers for post-therapeutic cicatrization time in monocytes from cutaneous leishmaniasis patients.

Cutaneous leishmaniasis (CL) treatment is based on therapy with Glucantime® , yet, there are few laboratory methods to monitor its success. In this study, ex vivo and in vitro evaluations of peripheral blood monocytes were performed in a longitudinal study to characterize the impact of Glucantime® on overall phenotypic/functional features of these cells from CL patients to identify predictive biomarkers for post-therapeutic monitoring by flow cytometry. The ex vivo evaluation from CL patients demonstrated a modulatory profile before treatment, with a decrease in TLR-2, FcγRII, HLA-DR, CD86, IFN-γR, TNF, IL-12, NO, and an increase in FcγRIII and IL-10R. Conversely, treatment changes some of these biomarker expressions by decreasing FcγRIII and IL-10R and increasing IFN-γR, IL-12 and NO. Moreover, an in vitro analysis of these patients showed a reduced phagocytic capacity of Leishmania braziliensis and higher levels of IL-10 and TGF-ß modulating functional profile. Regardless of the compromised L. braziliensis phagocytic capacity, treatment re-established the production of IL-12, IL-10, TGF-ß and NO at the basal level. Notably, monocytes from patients with early cicatrization showed enhanced FcγRI and FcγRII expressions and reduced IL-10, which was further corroborated by a baseline fold change analysis. Finally, the logistic regression model emphasized the performance of FcγRI, FcγRII and IL-10 as robust predictive biomarkers for post-therapeutic cicatrization during cutaneous leishmaniasis.

Response of high-risk of recurrence/progression bladder tumours expressing sialyl-Tn and sialyl-6-T to BCG immunotherapy.

BACKGROUND: High risk of recurrence/progression bladder tumours is treated with Bacillus Calmette-Guérin (BCG) immunotherapy after complete resection of the tumour. Approximately 75% of these tumours express the uncommon carbohydrate antigen sialyl-Tn (Tn), a surrogate biomarker of tumour aggressiveness. Such changes in the glycosylation of cell-surface proteins influence tumour microenvironment and immune responses that may modulate treatment outcome and the course of disease. The aim of this work is to determine the efficiency of BCG immunotherapy against tumours expressing sTn and sTn-related antigen sialyl-6-T (s6T). METHODS: In a retrospective design, 94 tumours from patients treated with BCG were screened for sTn and s6T expression. In vitro studies were conducted to determine the interaction of BCG with high-grade bladder cancer cell line overexpressing sTn. RESULTS: From the 94 cases evaluated, 36 had recurrence after BCG treatment (38.3%). Treatment outcome was influenced by age over 65 years (HR=2.668; (1.344-5.254); P=0.005), maintenance schedule (HR=0.480; (0.246-0.936); P=0.031) and multifocality (HR=2.065; (1.033-4.126); P=0.040). sTn or s6T expression was associated with BCG response (P=0.024; P<0.0001) and with increased recurrence-free survival (P=0.001). Multivariate analyses showed that sTn and/or s6T were independent predictive markers of recurrence after BCG immunotherapy (HR=0.296; (0.148-0.594); P=0.001). In vitro studies demonstrated higher adhesion and internalisation of the bacillus to cells expressing sTn, promoting cell death. CONCLUSION: s6T is described for the first time in bladder tumours. Our data strongly suggest that BCG immunotherapy is efficient against sTn- and s6T-positive tumours. Furthermore, sTn and s6T expression are independent predictive markers of BCG treatment response and may be useful in the identification of patients who could benefit more from this immunotherapy.

Autoantibodies to MUC1 glycopeptides cannot be used as a screening assay for early detection of breast, ovarian, lung or pancreatic cancer.

BACKGROUND: Autoantibodies have been detected in sera before diagnosis of cancer leading to interest in their potential as screening/early detection biomarkers. As we have found autoantibodies to MUC1 glycopeptides to be elevated in early-stage breast cancer patients, in this study we analysed these autoantibodies in large population cohorts of sera taken before cancer diagnosis. METHODS: Serum samples from women who subsequently developed breast cancer, and aged-matched controls, were identified from UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) and Guernsey serum banks to formed discovery and validation sets. These were screened on a microarray platform of 60mer MUC1 glycopeptides and recombinant MUC1 containing 16 tandem repeats. Additional case-control sets comprised of women who subsequently developed ovarian, pancreatic and lung cancer were also screened on the arrays. RESULTS: In the discovery (273 cases, 273 controls) and the two validation sets (UKCTOCS 426 cases, 426 controls; Guernsey 303 cases and 606 controls), no differences were found in autoantibody reactivity to MUC1 tandem repeat peptide or glycoforms between cases and controls. Furthermore, no differences were observed between ovarian, pancreatic and lung cancer cases and controls. CONCLUSION: This robust, validated study shows autoantibodies to MUC1 peptide or glycopeptides cannot be used for breast, ovarian, lung or pancreatic cancer screening. This has significant implications for research on the use of MUC1 in cancer detection.

Correspondence between performance of Eucalyptus spp trees selected from family and clonal tests.

We examined the correspondence in performance between trees selected from a family test and their respective clones from a clonal test of Eucalyptus. Full-sib families were obtained from controlled pollination among individuals of Eucalyptus grandis and between E. grandis and E. urophylla. The hybridizations did not follow a factorial scheme. The family tests were carried out at three locations in Eunápolis and Itabela counties, in Bahia, Brazil, in 2003. Four hundred and ninety-seven high-performance trees were selected, by the individual BLUP procedure, in the family tests at two years of age, based on wood volume. The clones from these trees and 14 checks were evaluated in clonal tests carried out in the same region in 2006. The wood volume of the clones was evaluated at two years of age. Trait correlation between the trees selected from the family and clonal tests was low. The estimate of the coincidence between the best trees and the best clones using an average of the different intensities of selection was only 27%. These results demonstrate that the selection of trees in the family test should not be too drastic; otherwise the chance plus clones may be overlooked.

Spatial and temporal changes in cell proliferation in the chick jejunum during the folding of the ridges into zigzags.

Vilification in the chick gut involves the formation of longitudinal ridges, establishment of their zigzag pattern and emergence of individual villi. Although the morphological changes during vilification are well known in the chick gut, the pattern of cell proliferation during this process is poorly understood. The aim of the present study was to correlate spatial and temporal changes in cell proliferation to folding of the longitudinal ridges into zigzags. Embryos on the 13th pos-incubation day were injected with BrdU and sacrificed at 8 h intervals up to 64 h after injection. Spatial and temporal changes in cell proliferation were observed during the folding the longitudinal ridges into zigzags. Cell proliferation occurred throughout the epithelium of the folded ridges, was predominant in the epithelial cells at the sides of the zigzagging ridges, and finally appeared in the epithelial cells at the tips of the zigzag ridges. In conclusion, cell proliferation might be a requirement for the folding of the longitudinal ridges into zigzags.

Different expression levels of alpha3/4 fucosyltransferases and Lewis determinants in ovarian carcinoma tissues and cell lines.

Ovarian carcinoma is the leading cause of death from gynecological cancers in many countries. Fucosylated glycoconjugates have been associated with various carcinomas. In the present study, we have characterized the expression of alpha3/4 fucosyltransferases transcripts and their products, the Lewis carbohydrate determinants, and their in vitro specificity towards synthetic acceptors using ovarian carcinoma cell lines OVM, m130, GG and SKOV3. We found different expression patterns: GG cells expressed mostly Lewisx (Lex), Lewisy (Ley), sLea and Leb, and m130 cells expressed mostly Lex and Ley. The detection was on the plasma membrane and in intracellular vesicles. OVM and SKOV3 cells had very low amounts of staining. From RT-PCR studies, enzyme specificity of cellular extracts towards a panel of synthetic carbohydrate acceptors and Western blot analysis we concluded that Lea, sLea and Leb were synthesised by FUT3, whereas Lex and Ley were synthesized by FUT4 and FUT9 in both cell lines. The GG and m130 cell lines are adequate models to investigate the role of Lex, Ley, sLea and Leb in ovarian carcinoma development.

Loss of a novel mucin-like epithelial glycoprotein in oral and cervical squamous cell carcinomas.

Stratified squamous epithelia of oral and cervical mucosa express high levels of simple mucin-type O-linked carbohydrates, and these are known to undergo structural changes in relation to epithelial differentiation and neoplastic transformation. O-glycans in these epithelia are associated with the cell membrane, but the identity of the carrier molecule(s) remains largely unknown. We report here the identification of a membrane-bound M(r) 200,000-250,000 glycoprotein (gp230) that is expressed in stratified squamous epithelia of the oral cavity. Western blot analysis identified gp230 as a major carrier of simple-mucin type carbohydrate antigens in buccal nonkeratinized mucosal epithelium, suggesting that it may represent a mucin-like molecule. A monoclonal antibody PANH4 defining a protein epitope of gp230 was generated. The PANH4 epitope was localized by immunohistology to suprabasal cell layers of buccal epithelium and was also found in larynx, esophagus, vagina, and exocervix, but not in epidermis. Data showed that gp230 was distinct from MUC1 or CD44. It is interesting that in most cases gp230 was not expressed in squamous cell carcinomas of buccal and cervical mucosa. A few moderately differentiated carcinomas, mainly from cervix, expressed the gp230 epitope. The results suggest that a membrane-bound mucin-like molecule, gp230, is associated with the differentiated phenotype of normal mucosal stratified squamous epithelia and that expression of gp230 generally is lost in severe oral epithelial dysplasia and squamous cell carcinomas of oral and cervical mucosa.

Intestinal metaplasia of human stomach displays distinct patterns of mucin (MUC1, MUC2, MUC5AC, and MUC6) expression.

Intestinal metaplasia is a well-established premalignant condition of the stomach that is characterized by mucin carbohydrate modifications defined by histochemical methods. The purpose of the present study was to see whether the expression of mucin core proteins was modified in the different types of intestinal metaplasia and to evaluate the putative usefulness of mucins as "molecular markers" in this setting. We used a panel of monoclonal antibodies with well-defined specificities to MUC1, MUC2, MUC5AC, and MUC6 to characterize the expression pattern of mucins. In contrast to normal gastric mucosa, the complete form or type I intestinal metaplasia (n = 20) displayed little or no expression of MUC1, MUC5AC, or MUC6 in the metaplastic cells and strong expression of the intestinal mucin MUC2 in the goblet cells of all cases. The incomplete forms of intestinal metaplasia, type II (n = 25) and type III (n = 16), expressed MUC1 and MUC5AC in every case, both in goblet and in columnar cells. MUC6 was also expressed in 16 cases of type II intestinal metaplasia and in 11 cases of type III intestinal metaplasia. The intestinal mucin MUC2 was expressed in every case of incomplete intestinal metaplasia, mostly in goblet cells. The mucin expression profile in the different types of intestinal metaplasia allows the identification of two patterns: one defined by decreased levels of expression of "gastric" mucins (MUC1, MUC5AC, and MUC6) and expression of MUC2 intestinal mucin, which corresponds to type I intestinal metaplasia, and the other defined by coexpression of "gastric mucins" (MUC1, MUC5AC, and MUC6) together with the MUC2 mucin, encompassing types II and III intestinal metaplasia. Our results challenge the classical sequential pathway of intestinal metaplasia (from type I to type III via a type II intermediate step).

Canine Gastric Pathology: A Review.

Gastric disorders are common in dogs and are a major reason for veterinary consultation. In human medicine, the classification of gastric diseases based on histological features, genotypes and molecular phenotypes helps to better understand the characteristics of each subtype, and to improve early diagnosis, prevention and treatment. Canine gastric lesions often show strong histological similarities to their human counterparts. However, such conditions in the canine stomach are poorly studied and their cellular and molecular features are largely unknown. This article reviews the histopathological classification of inflammatory and neoplastic lesions of the canine stomach and provides an update on the application of molecular techniques within the field of canine gastric pathology. The canine disorders are compared with current knowledge of the equivalent human diseases.

Preventing E-cadherin aberrant N-glycosylation at Asn-554 improves its critical function in gastric cancer.

E-cadherin is a central molecule in the process of gastric carcinogenesis and its posttranslational modifications by N-glycosylation have been described to induce a deleterious effect on cell adhesion associated with tumor cell invasion. However, the role that site-specific glycosylation of E-cadherin has in its defective function in gastric cancer cells needs to be determined. Using transgenic mice models and human clinical samples, we demonstrated that N-acetylglucosaminyltransferase V (GnT-V)-mediated glycosylation causes an abnormal pattern of E-cadherin expression in the gastric mucosa. In vitro models further indicated that, among the four potential N-glycosylation sites of E-cadherin, Asn-554 is the key site that is selectively modified with ß1,6 GlcNAc-branched N-glycans catalyzed by GnT-V. This aberrant glycan modification on this specific asparagine site of E-cadherin was demonstrated to affect its critical functions in gastric cancer cells by affecting E-cadherin cellular localization, cis-dimer formation, molecular assembly and stability of the adherens junctions and cell-cell aggregation, which was further observed in human gastric carcinomas. Interestingly, manipulating this site-specific glycosylation, by preventing Asn-554 from receiving the deleterious branched structures, either by a mutation or by silencing GnT-V, resulted in a protective effect on E-cadherin, precluding its functional dysregulation and contributing to tumor suppression.

Immunohistochemical study of the expression of MUC6 mucin and co-expression of other secreted mucins (MUC5AC and MUC2) in human gastric carcinomas.

To investigate the expression of MUC6 mucin in gastric carcinomas, we generated a novel monoclonal antibody (MAb CLH5) using an MUC6 synthetic peptide. MAb CLH5 reacted exclusively with the MUC6 peptide and with native and deglycosylated mucin extracts from gastric tissues. MAb CLH5 immunoreactivity was observed in normal gastric mucosa restricted to pyloric glands of the antrum and mucopeptic cells of the neck zone of the body region. In a series of 104 gastric carcinomas, 31 (29.8%) were immunoreactive for MUC6. The expression of MUC6 was not associated with histomorphological type or with clinicopathological features of the carcinomas. Analysis of the co-expression of MUC6 with other secreted mucins (MUC5AC and MUC2) in 20 gastric carcinomas revealed that different mucin core proteins are co-expressed in 55% of the cases. MUC6 was co-expressed and co-localized with MUC5AC in 45% and with MUC2 in 5% of the cases. Expression of MUC2 alone was observed in 25% of the cases. All carcinomas expressing MUC2 mucin in more than 50% of the cells were of the mucinous type according to the WHO classification. The co-expression of mucins was independent of the histomorphological type and stage of the tumors. In conclusion, we observed, using a novel well-characterized MAb, that MUC6 is a good marker of mucopeptic cell differentiation and is expressed in 30% of gastric carcinomas, independent of the clinicopathological features of the cases. Furthermore, we found that co-expression and co-localization of mucins in gastric carcinomas is independent of histomorphology and staging. Finally, we observed that intestinal mucin MUC2 is expressed as the most prominent mucin of the mucins tested in mucinous-type gastric carcinomas.

MUC5B expression in gastric carcinoma: relationship with clinico-pathological parameters and with expression of mucins MUC1, MUC2, MUC5AC and MUC6.

Previous studies have shown that mucin expression can be used to evaluate differentiation patterns of gastric carcinoma: MUC5AC expression is associated with diffuse type and early gastric carcinomas, and MUC2 expression is associated with mucinous gastric carcinomas. The role played by MUC5B in the evaluation of differentiation and biological behaviour of gastric carcinoma is largely unknown. Our aim was to characterise the pattern of expression of mucins MUC1, MUC2, MUC5AC, MUC5B and MUC6 in a series of 50 gastric carcinomas to evaluate whether MUC5B expression was associated with the clinico-pathological characteristics of the cases and/or with the co-expression of other mucins. A panel of six monoclonal antibodies (HMFG1, SM3, PMH1, CLH2, EU-MUC5Ba and CLH5) was used to determine the expression of mucins (MUC1, MUC1 underglycosylated form, MUC2, MUC5B, MUC5AC and MUC6, respectively) using immunohistochemistry. Cases were considered positive if more than 5% of the cells expressed immunoreactivity for the several mucins evaluated. Our results showed that: (a) expression of MUC5B was observed in 11 cases (22.0%) and was associated with the "unclassified" histological type of gastric carcinoma according to Laurén ( P = 0.03) and with the absence of venous invasion ( P = 0.02); (b) in this series, MUC5B expression had no impact on survival of patients with gastric carcinoma; (c) the expression of MUC5B was associated with the co-expression of MUC5AC ( P = 0.02) and (d) none of the cases with the so-called complete intestinal phenotype of mucin expression expressed MUC5B.

Immunohistochemical study of the expression of MUC5AC and MUC6 in breast carcinomas and adjacent breast tissues.

AIM: To study the protein expression patterns of MUC5AC and MUC6 in normal and diseased breast tissues and to compare their expression with that of a mucin (MUC1) normally expressed in mammary tissues. METHODS: Formalin fixed, paraffin wax embedded tissue from 69 cases of invasive breast carcinoma and surrounding breast tissue was studied immunohistochemically with monoclonal antibodies against MUC1 (SM3), MUCSAC (CLH2), and MUC6 (CLH6), using the avidin-biotin-peroxidase method. RESULTS: MUC5AC was detected in five of 68 cases of invasive carcinoma including one of three cases of pure colloid carcinoma. MUCSAC expression in the adjacent normal breast epithelium was present in one of 29 cases and in one of two cases of ductal carcinoma in situ. None of 15 cases of ductal hyperplasia without atypia was positive for MUCSAC. MUC6 was present in 15 of 65 cases of invasive carcinoma, in four of 29 cases of normal adjacent epithelium, two of 15 cases of ductal hyperplasia without atypia, and one of two cases of ductal carcinoma in situ. MUC1 immunoreactivity detected by the SM3 antibody was present in 50 of the 67 cases of invasive carcinoma, but expression was also detected in benign epithelium. All invasive carcinomas expressing MUCSAC were positive for MUC1 and four were positive for MUC6. No significant association was found between the expression of these mucins and tumour size, histological grade, node status, oestrogen receptor status, p53 positivity, or c-ErbB-2 overexpression. CONCLUSIONS: This study documents the expression of two different mucins (MUCSAC and MUC6) not described as being expressed by normal breast tissues in a minority of breast carcinomas, as well as in normal and hyperplastic epithelium. Although the role of mucins in malignant transformation and the progression of breast cancer is not well understood, in some cases, there is probably an upregulation of several genes that encode distinct mucin proteins.

Mucins and mucin-associated carbohydrate antigens expression in gastric carcinoma cell lines.

Mucins are high-molecular-mass glycoproteins with high carbohydrate content and marked heterogeneity both in the apoprotein and in the oligosaccharide side chains. Mucin genes are expressed in a regulated manner, namely in the human stomach. The first aim of the present study was to characterise the expression of mucins and mucin-associated carbohydrate antigens in seven gastric carcinoma cell lines, and to compare their expression profiles with those of normal gastric tissues and human gastric carcinomas. Secondly, we aimed to see whether or not there is an association between the expression of mucins and mucin-associated carbohydrate antigens. Our results show that mucin expression in gastric carcinoma cell lines: (a) follows in part the mucin expression profile of normal gastric mucosa and gastric carcinomas with wide expression of MUC1 and MUC5AC; (b) parallels the aberrant pattern of mucin expression observed in human gastric carcinomas with occasional expression of MUC2, MUC3, MUC4 and MUC5B; (c) does not include, at least in our series, the expression of MUC6 mucin; and (d) follows in part the differentiation pattern of the carcinomas from which the cell lines originated, keeping S-Tn expression in cell lines derived from glandular carcinomas. Our results further demonstrate that there is no apparent relationship between the mucin core proteins and the simple mucin-type or Lewis carbohydrate antigens.

Expression and localization of immunoreactive-sialomucin complex (Muc4) in salivary glands.

Sialomucin Complex (SMC; Muc4) is a heterodimeric glycoprotein consisting of two subunits, the mucin component ASGP-1 and the transmembrane subunit ASGP-2. Northern blot and immunoblot analyses demonstrated the presence of SMC/Muc4 in submaxillary, sublingual and parotid salivary glands of the rat. Immunocytochemical staining of SMC using monoclonal antisera raised against ASGP-2 and glycosylated ASGP-1 on paraffin-embedded sections of parotid, submaxillary and sublingual tissues was performed to examine the localization of the mucin in the major rat salivary glands. Histological and immunocytochemical staining of cell markers showed that the salivary glands consisted of varying numbers of serous and mucous acini which are drained by ducts. Parotid glands were composed almost entirely of serous acini, sublingual glands were mainly mucous in composition and a mixture of serous and mucous acini were present in submaxillary glands. Since immunoreactive (ir)-SMC was specifically localized to the serous cells, staining was most abundant in parotid glands, intermediate levels in submaxillary glands and least in sublingual glands. Ir-SMC in sublingual glands was localized to caps of cells around mucous acini, known as serous demilunes, which are also present in submaxillary glands. Immunocytochemical staining of SMC in human parotid glands was localized to epithelial cells of serous acini and ducts. However, the staining pattern of epithelial cells was heterogeneous, with ir-SMC present in some acinar and ductal epithelial cells but not in others. This report provides a map of normal ir-SMC/Muc4 distribution in parotid, submaxillary and sublingual glands which can be used for the study of SMC/Muc4 expression in salivary gland tumors.

Atomic force microscopy measurements reveal multiple bonds between Helicobacter pylori blood group antigen binding adhesin and Lewis b ligand.

The strength of binding between the Helicobacter pylori blood group antigen-binding adhesin (BabA) and its cognate glycan receptor, the Lewis b blood group antigen (Le(b)), was measured by means of atomic force microscopy. High-resolution measurements of rupture forces between single receptor-ligand pairs were performed between the purified BabA and immobilized Le(b) structures on self-assembled monolayers. Dynamic force spectroscopy revealed two similar but statistically different bond populations. These findings suggest that the BabA may form different adhesive attachments to the gastric mucosa in ways that enhance the efficiency and stability of bacterial adhesion.

Bioengineered surfaces promote specific protein-glycan mediated binding of the gastric pathogen Helicobacter pylori.

Helicobacter pylori colonizes the gastric mucosa of half of the worlds population and persistent infection is related with an increase in the risk of gastric cancer. Adhesion of H. pylori to the gastric epithelium, which is essential for infection, is mediated by bacterial adhesin proteins that recognize specific glycan structures (Gly-R) expressed in the gastric mucosa. The blood group antigen binding adhesin (BabA) recognizes difucosylated antigens such as Lewis B (Leb), while the sialic acid binding adhesin (SabA) recognizes sialylated glycoproteins and glycolipids, such as sialyl-Lewis x (sLex). This work aimed to investigate whether these Gly-Rs (Leb and sLex) can attract and specifically bind H. pylori after immobilization on synthetic surfaces (self-assembled monolayers (SAMs) of alkanethiols on gold). Functional bacterial adhesion assays for (Gly-R)-SAMs were performed using H. pylori strains with different adhesin protein profiles. The results demonstrate that H. pylori binding to surfaces occurs via interaction between its adhesins and cognate (Gly-R)-SAMs and bound H. pylori maintains its characteristic rod-shaped morphology only during conditions of specific adhesin-glycan binding. These results offer new insights into innovative strategies against H. pylori infection based on the scavenging of bacteria from the stomach using specific H. pylori chelating biomaterials.

Mucin 6 and Tn antigen expression in canine mammary tumours: correlation with pathological features.

Overexpression of mucins is known to decrease cell-to-cell adhesion and thus to facilitate the invasion of cancer cells through the extracellular matrix. Mucin 6 (MUC6) is overexpressed and aberrantly O-glycosylated in human breast cancer, serving as a carrier for one of the most specific cancer-associated antigens, Tn antigen. Despite its relevance in breast cancer, MUC6 expression has not yet been characterized in canine mammary tumours (CMTs). The aims of this study were to assess the expression of MUC6 and Tn antigen in 55 benign and 77 malignant CMTs of different histological types and to investigate possible correlations with pathological features. MUC6 and Tn antigen were found to be significantly overexpressed in malignant compared with benign CMTs. MUC6 was significantly overexpressed in simple and complex carcinomas compared with simple and complex adenomas, respectively. When considering only the epithelial population, significant MUC6 overexpression was observed in carcinosarcomas when compared with benign mixed tumours. In addition, MUC6 was significantly overexpressed in simple compared with complex carcinomas. Finally, double-labelling immunofluorescence performed on seven malignant CMTs showed MUC6 and Tn co-expression. Therefore, MUC6 and Tn antigen overexpression is associated with malignant phenotypes of CMTs.

First-degree relatives of patients with early-onset gastric carcinoma show even at young ages a high prevalence of advanced OLGA/OLGIM stages and dysplasia.

BACKGROUND: First-degree relatives (FDRs) of early-onset gastric carcinoma (EOGC) patients are at increased risk of cancer development. OLGA/OLGIM (Operative Link on Gastritis/Intestinal Metaplasia Assessment) classifications have been proposed for the identification of individuals at high risk of gastric cancer development. AIM: To estimate the prevalence and severity of premalignant conditions and lesions in FDRs of EOGC patients. METHODS: A case-control study was conducted encompassing 103 FDRs of EOGC patients (cases) and 101 age- and gender-matched controls, all submitted to upper GI endoscopy and OLGA and OLGIM used for staging as well as modified versions with exclusion of the biopsies from incisura angularis in the analysis. RESULTS: Helicobacter pylori infection was present in 82% of cases (P = 0.001). Atrophy was present in 70% of cases (OLGA stages I-IV). High-risk stages (III-IV) were identified only in cases (19%) (P < 0.001). Dysplasia was diagnosed only in cases (n = 7, P = 0.007). The application of OLGIM, modified OLGA and modified OLGIM classifications led to downgrade of stages in comparison with the original OLGA classification (27%, 15% and 30% respectively). In all classification systems, dysplastic lesions clustered (86%) in high-risk stages. CONCLUSIONS: FDRs of EOGC patients have, even at young ages, a high prevalence of H. pylori infection, high-risk OLGA and OLGIM stages and dysplasia. These patients should undergo accurate endoscopic observation with at least four biopsies in antrum and corpus to allow adequate staging and follow-up of premalignant conditions and lesions scored in high-risk stages, in accordance with international guidelines recently proposed.

Helicobacter pylori adhesion to gastric epithelial cells is mediated by glycan receptors.

Helicobacter pylori adhesion to gastric epithelial cells constitutes a key step in the establishment of a successful infection of the gastric mucosa. The high representation of outer membrane proteins in the bacterial genome suggests the relevance of those proteins in the establishment of profitable interactions with the host gastric cells. Gastric epithelial cells are protected by a mucous layer gel, mainly consisting of the MUC5AC and MUC6 mucins. In addition to this protective role, mucins harbor glycan-rich domains that constitute preferential binding sites of many pathogens. In this article we review the main players in the process of H. pylori adhesion to gastric epithelial cells, which contribute decisively to the high prevalence and chronicity of H. pylori infection. The BabA adhesin recognizes both H-type 1 and Lewis b blood-group antigens expressed on normal gastric mucosa of secretor individuals, contributing to the initial steps of infection. Upon colonization, persistent infection induces an inflammatory response with concomitant expression of sialylated antigens. The SabA adhesin mediates H. pylori binding to inflamed gastric mucosa by recognizing sialyl-Lewis a and sialyl-Lewis x antigens. The expression of the BabA and SabA adhesins is tightly regulated, permitting the bacteria to rapidly adapt to the changes of glycosylation of the host gastric mucosa that occur during infection, as well as to escape from the inflammatory response. The growing knowledge of the interactions between the bacterial adhesins and the host receptors will contribute to the design of alternative strategies for eradication of the infection.