Expression profile of mucins (MUC2, MUC5AC and MUC6) in Helicobacter pylori infected pre-neoplastic and neoplastic human gastric epithelium

BACKGROUND: Helicobacter pylori (H. pylori) causes gastritis and intestinal metaplasia (IM) that may evolve to gastric carcinoma. The objective of this study was to compare the profile of mucins in the progressive stages of H. pylori infected pre-neoplastic and neoplastic human gastric epithelium. We used a panel of monoclonal antibodies with well-defined specificities of MUC2, MUC5AC and MUC6 to characterize the expression pattern of mucins by immunohistochemistry. METHODS: RUT and ELISA were down for H. pylori confirmation. Human gastric biopsy sections were stained using immunohistochemistry with MUC2, MUC5AC and MUC6 antibodies. RESULTS: MUC5AC was expressed in the superficial epithelium and the upper part of the gastric pits. MUC6 expression was detected in the lower part of the gastric glands. MUC2 was expressed in intestinal metaplasia, mostly in goblet cells. The mucin expression profile in the progressive stages of H. pylori infected human gastric epithelium allows the identification of intestinal metaplasia, which is characterized by a decreased expression of the gastric mucins (MUC5AC and MUC6) and de novo expression of MUC2. CONCLUSION: In conclusion, our results suggest that there is altered expression of MUC5AC and MUC6 together with the aberrant expression of MUC2 in intestinal metaplasia, during the process of gastric carcinogenesis. The present study indicates that the MUC2 mucin expression pattern is a reliable marker of intestinal metaplasia, which appears in the context of H. pylori infected individuals

Expression of MUC5AC in normal gastric mucosa, intestinal metaplasia and gastric carcinoma by immunohistochemistry

Background: Carcinomas of the stomach are a heterogeneous group of lesions in terms of architecture, pattern of growth, cell differentiation, and histogenesis. Altered MUC5AC expression patterns have been reported previously in intestinal metaplasia as well as in gastric cancer. The aim of the study was to analyse the expression pattern of MUC5AC in normal, pre-neoplastic and neoplastic gastric epithelium.Methods: Formalin fixed paraffin embedded sections of sixty cases which include twenty cases of each normal gastric mucosa, intestinal metaplasia and gastric carcinoma were taken up for the study and subjected to immunohistochemistry using MUC5AC.Results: The intensity of MUC5AC immunostaining in normal gastric mucosa, intestinal metaplasia and gastric carcinoma was evaluated. Immunoreactivity was graded as 0 (negative), ± (trace positive), + (positive) or ++ (strongly positive). Statistical analysis was performed with Chi-Square test and significant differences were noted between these 3 groups (p value <0.05).Conclusions: Authors concluded that MUC5AC expression rates might be good parameters in progression of intestinal metaplasia to gastric carcinoma and might be a good prognostic marker for gastric carcinoma as it is very well implicated in understanding of gastric carcinogenesis

Mucin expression in normal and diseased states of the stomach : a histochemical and immunohistochemical study

Nine human mucin genes have been described, which express glycoproteins MUCJ,2,3,4 ,5AC,5B,6, 7, and 8 in various tissues. It has been shown that different mucins are expressed in various gastric disease states as compared to the normal. In this study histochemical and immunohistochemical methods were used to determine the type of mucin and the pattern of staining in 54 patients with a variety of gastric conditions [i.e. normal controls, foetal stomachs, chronic active gastritis, low grade dysplasia, intestinal metaplasia (associated with gastritis, benign ulcers, dysplasia and cancer), early and advanced intestinal type adenocarcinoma, and diffuse adenocarcinoma]. MUCJ-7 antibodies were used in the study, this being the first study to all assess seven MUC antibodies in the various conditions. It is also the first study to assess the pattern of mucin staining in foetal stomachs. Normal controls were immunoreactive for MUC4, 5 and 6, and gastritis specimens showed similar results, although the latter showed more MUCJ immunoreactivity. Whereas early foetal stomach showed no MUC immunoreactivity, MUC4, 5 and 6 were present from the early second trimester onwards. There was no significant difference between dysplasia and intestinal metaplasia, both categories showing expression of MUC2 and 3 predominantly. Early intestinal type adenocarcinomas did not show any mucins in the majority of cases. Advanced intestinal type adenocarcinomas showed immunoreactivity predominantly for MUCJ, 5 and 6, as well as MUC2 in some cases. Diffuse adenocarcinomas showed strong positive MUC2 and MUC6 staining, and in some cases MUC5 and 7. In conclusion this study has shown different patterns of mucin immunoreactivity in various gastric disease states. Specimens with dysplasia, intestinal metaplasia, late intestinal type adenocarcinoma and diffuse gastric cancer were characterized by increased diversity of mucin gene expression, whereas early intestinal cancer showed loss of mucin immunoreactivity

Mucin pattern reflects the origin of the adenocarcinoma in Barrett's esophagus: a retrospective clinical and laboratorial study

<p>Abstract</p> <p>Background</p> <p>Mucin immunoexpression in adenocarcinoma arising in Barrett's esophagus (BE) may indicate the carcinogenesis pathway. The aim of this study was to evaluate resected specimens of adenocarcinoma in BE for the pattern of mucins and to correlate to the histologic classification.</p> <p>Methods</p> <p>Specimens were retrospectively collected from thirteen patients who underwent esophageal resection due to adenocarcinoma in BE. Sections were scored for the grade of intestinal metaplasia. The tissues were examined by immunohistochemistry for MUC2 and MUC5AC antibodies.</p> <p>Results</p> <p>Eleven patients were men. The mean age was 61 years old (varied from 40 to 75 years old). The tumor size had a mean of 4.7 ± 2.3 cm, and the extension of BE had a mean of 7.7 ± 1.5 cm. Specialized epithelium with intestinal metaplasia was present in all adjacent mucosas. Immunohistochemistry for MUC2 showed immunoreactivity in goblet cells, while MUC5AC was extensively expressed in the columnar gastric cells, localizing to the surface epithelium and extending to a variable degree into the glandular structures in BE. Tumors were classified according to the mucins in gastric type in 7/13 (MUC5AC positive) and intestinal type in 4/13 (MUC2 positive). Two tumors did not express MUC2 or MUC5AC proteins. The pattern of mucin predominantly expressed in the adjacent epithelium was associated to the mucin expression profile in the tumors, p = 0.047.</p> <p>Conclusion</p> <p>Barrett's esophagus adenocarcinoma shows either gastric or intestinal type pattern of mucin expression. The two types of tumors developed in Barrett's esophagus may reflect the original cell type involved in the malignant transformation.</p

Immunohistochemical Profile of Mucins and their Expression in Precancerous Changes of the Stomach

The aim of this study was to assess the profile of mucins (MUC1, MUC2, MUC5AC) in the intestinal metaplasia (IM) of the gastric mucosa through the immunohistochemical method. Methods: To identify the metaplastic areas in the gastric mucosa, chromoendoscopy was employed using 0.5% solution of methylene blue. The expression of the profile of the mucins was determined using immunohistochemistry with MUC1, MUC5AC, and MUC2 antibodies (clone Ma695, clone CLH2, Ccp58 and CLH5, "Novocastra "Great Britain). Results: In the regions adjacent to the adenocarcinoma and neoplastic modified cells, a visible weak expression of MUC2 and MUC5AC was observed. In the case of complete IM, a visibly maximum MUC2 expression was observed in the goblet cells; thus, the MUC5AC, MUC1, and MUC6 marking were absent in the columnar epitheliocytes with the brush border. In the case of incomplete IM, along with the positive MUC2 markings of the goblet cells, the presence of gastric mucin (MUC5AC) has been observed in 25% of such patients with chronic atrophic gastritis (CAG) having incomplete IM; however, in the columnar epitheliocytes the characteristic occurrence of gastric mucin (MUC5AC) was observed in 100% of the patients while a small amount of MUC2 was recorded in 15% of patients. Conclusion: The MUC5AC expression of the gastric mucins in the columnar epithelial cells and the goblet exocrinocytes marks the formation of the gastrointestinal phenotype viz., incomplete intestinal metaplasia, along with the simultaneous production of the MUC2 by the goblet cells. The decrease with further loss of the protective MUC5AC production by the columnar epithelial cells and goblet exocrinocytes that were found in the regions of severe dysplasia and IM, adjacent to the neoplastic altered cells, may serve as additional criteria of early malignancy of the gastric mucosa

Izraženost glikoproteinskog antitijela MUC2 i vaskularnog endotelnog čimbenika rasta (VEGF) u sluznici Barrettova jednjaka

Higher expression of the mucin 2 (MUC2) glycoprotein and vascular endothelial growth factor (VEGF) in Barrett’s mucosa may be associated with a higher risk of esophageal adenocarcinoma development. Thirty-six patients diagnosed with Barrett’s esophagus (BE), short-segment, were included in the study due to unsuccessful treatment with proton pump inhibitors. The diagnosis was confirmed by histopathologic analysis of the tissue obtained by esophagogastric junction biopsy. Expression of MUC2 and VEGF was determined by immunohistochemistry. We found four patients in early stage of adenocarcinoma and 32 patients with BE; five of them had indication for argon plasma coagulation treatment, one for radiofrequency ablation and one for endoscopic mucosal resection; 25 patients were treated with proton pump inhibitors. Regression of BE occurred in 25 (69.44%) patients. MUC2 positivity is unique for goblet cells in patients with BE, but it is not the only marker. VEGF is an indicator of angiogenesis in the mucosa of patients with BE and adenocarcinoma.Izražajnost glikoproteina mucina 2 (MUC2) i vaskularnog endotelnog faktora rasta (VEGF) u sluznici Barrettova jednjaka (BJ) može se dovesti u vezu s višim rizikom razvoja adenokarcinoma jednjaka. Studija je obuhvatila 36 bolesnika s dijagnozom BJ koja je potvrđena patohistološkom analizom nakon višestrukih biopsija ezofagogastričnog spoja. Izražajnost MUC2 i VEGF-a je prikazana imunohistokemijskom analizom. Otkrivena su četiri bolesnika u ranom stadiju adenokarcinoma (učinjena je totalna ezofagektomija) i 32 bolesnika s BJ, od kojih je petoro imalo indikaciju za argon plazma koagulaciju, jedan za endoskopsku resekciju sluznice, jedan za radiofrekventnu ablaciju, a 25 ih je liječeno inhibitorima protonske pumpe. Regresija BJ je zabilježena u 25 (69,44%) bolesnika. Pozitivan nalaz MUC2 je karakterističan za vrčaste stanice u BJ, ali nije jedini biljeg. VEGF je pokazatelj angiogeneze u sluznici bolesnika s BJ i adenokarcinomom

Does CDX2 expression predict Barrett's metaplasia in oesophageal columnar epithelium without goblet cells?

Background: Intestinal metaplasia (Barrett's oesophagus), but not cardiac-type mucosa in columnar-lined oesophagus, is regarded as premalignant. As intestinal metaplasia and cardiac-type mucosa are endoscopically indiscernible, it is difficult to take targeted samples from columnar-lined oesophagus with consequently a risk of having undetected intestinal metaplasia. Aim: To investigate whether the intestinal markers CDX2, MUC2 and villin can predict the presence of undetected intestinal metaplasia in columnar-lined oesophagus. Methods: Presence of intestinal metaplasia or cardiac-type mucosa was identified in 122 biopsy sets of columnar-lined oesophagus from 61 patients, collected at two subsequent follow-up upper endoscopies. CDX2, MUC2 and villin expression were determined by immunohistochemistry. Results: All intestinal metaplasia samples (55) were positive for CDX2 and MUC2 and 32 of 55 for vil

An investigation of the development of a biochemical and clinical marker for gastric disease

Includes abstract. Includes bibliographical references