An Inverse Relationship between the Expression of the Gastric Tumor Suppressor RUNX3 and Infection with Helicobacter pylori in Gastric Epithelial Dysplasia

BACKGROUND/AIMS: This study was performed to determine the association between RUNX3 expression and Helicobacter pylori infection in premalignant gastric lesions. METHODS: We examined 107 patients with gastric epithelial dysplasia who had undergone endoscopic mucosal resection or submucosal dissection. All tissue samples were evaluated by RUNX3 staining and subclassified by immunophenotype. H. pylori infection in dysplastic lesions and the normal surrounding tissue was examined by silver staining, and cagA status was assessed by polymerase chain reaction. RESULTS: The loss of RUNX3 expression was observed in 62 cases (57.9%), and an association with H. pylori infection was found in 54 cases (50.5%). The infection rate with the cagA-positive H. pylori strain was 63.0%. In RUNX3-negative lesions, the rate of H. pylori infection (p=0.03) and the frequency of category 4 lesions (according to the revised Vienna classification) were high (p=0.02). In addition, the gastric mucin phenotype was predominant. In RUNX3-negative category 4 lesions, the rate of cagA-positive H. pylori infection rate was high but not significantly increased (p=0.08). CONCLUSIONS: Infection with H. pylori is associated with inactivation of RUNX3 in early gastric carcinogenesis. This mechanism was prominent in gastric cancer with a gastric mucin phenotype.

Clinicopathologic and immunohistochemical study on early gastric signet-ring cell carcinoma / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the expression of gastric and intestinal phenotypic markers in gastric signet-ring cell (SRC) carcinoma and the relationship with the clinicopathologic parameters and prognosis.</p><p><b>METHODS</b>Immunohistochemical study was carried out in 91 cases of early-stage SRC carcinoma using MUC1, MUC5AC and MUC6 antibodies as the gastric phenotypic markers and MUC2 and CDX2 antibodies as the intestinal phenotypic markers. According to the expression of phenotypic markers, the tumors were classified into three different subgroups: gastric, intestinal and mixed. The findings were analyzed together with various clinical parameters and follow-up data.</p><p><b>RESULTS</b>Amongst the 91 cases studied, 53 cases (58.2%) belonged to gastric type, 22 cases (24.2%) mixed type and 16 cases (17.6%) intestinal type. The positive rates of MUC2 and CDX2 in early submucosal carcinoma were significantly higher than those in mucosal carcinoma (P < 0.01). On the other hand, the rates of MUC5AC and MUC6 expression in early submucosal carcinoma were significantly lower than those in mucosal carcinoma (P < 0.01 and P < 0.05). The rates of MUC2 and CDX2 expression in cases with lymph node metastasis and vascular invasion were significantly higher than those in cases without nodal or vascular involvement (P < 0.05). The expression of CDX2 was also significantly higher in cases with larger tumor size (P < 0.05). Cases with intestinal phenotype more likely had invasion deeper than mucosal layer and carried higher chance of lymph node metastasis (P = 0.000 and P = 0.003). Intestinal and mixed types correlated with shortened five-year survival.</p><p><b>CONCLUSIONS</b>The intestinal type of SRC carcinoma is associated with poorer biologic behavior and prognosis, as compared with that of the gastric type. Classification on the basis of immunophenotypic markers may be useful in predicting prognosis and guiding treatment for patients with gastric SRC carcinoma.</p>

Mucin expression profile in Barrett's, dysplasia, adenocarcinoma sequence in the esophagus.

BACKGROUND: The molecular events that accompany the progression to adenocarcinoma (ADC) of the esophagus are poorly understood. Aberrant mucin receptor expression can contribute to increased cell growth and metastatic ability. AIM: The aim of this study was to establish a pattern for mucin (MUC) gene expression in the esophageal mucosa under normal and pathological conditions. SETTING: University Hospital Cancer Center Laboratory. Archived tissue samples studied in a retrospective fashion. MATERIALS AND METHODS: Tissue samples were obtained from the archives of patients with histological evidence of Barrett's esophagus (BE) progressing to ADC. Immunohistochemical analysis was performed using mouse monoclonal antibodies for MUC1, MUC2, MUC5AC, MUC6. Semiquantitative scoring of histological staining was performed using a linear scoring system: 0-staining absent; 1-staining in 0-25%; 2-staining in 25-50%; and 3-staining in 50-75% of the epithelium. The Binomial test was used to explore trends and differences in frequency of mucin expression along the pathological sequence. RESULTS: Only mild superficial staining of MUC1 was seen in normal squamous epithelium. MUC1 and MUC2 were uniformly expressed in all samples (7/7) of BE and dysplasia (P=0.008). MUC1 expression was upregulated (7/7) in progression to adenocarcinoma (P=0.008). The secretory mucins, MUC5AC and MUC6 showed a decrease in expression with progression from BE to dysplasia to ADC (P< 0.05). CONCLUSIONS: Downregulation of MUC5AC and MUC6 decreases mucosal protection against gastric acid. Increasing MUC1 expression is associated with progression from dysplasia to ADC. Upregulation of MUC2 reflects intestinal metaplasia in BE.

Expression of MUC3, MUC5AC, MUC6 and Epidermal Growth Factor Receptor in Gallbladder Epithelium according to Gallstone Composition / 대한소화기학회지

BACKGROUND/AIMS: Gallbladder (GB) mucin is one of the key factors in the gallstone formation. However, there is little information about the diversity of mucin secretion according to the stone composition. Epidermal growth factor receptor (EGFR) functions in proliferation including mucin secreting goblet cell hyperplasia. We compared the expressions of MUC3, MUC5AC, MUC6 and EGFR in the GB epithelium with cholesterol gallstones (GB-chol) group and pigment gallstones (GB-pig group). METHODS: GBs from elective laparoscopic cholecystectomy for the gallstone disease were studied. Stone composition was analyzed by the spectrophotometer. Immunohistochemical stain was performed using each monoclonal antibody. The percentage of stained proportion was scored by the NIH image program and the results were compared between both groups. RESULTS: Total 20 patients were enrolled (10 patients with cholesterol gallstones, 10 patients with pigment gallstones). The percentages of stained proportion for MUC3, MUC5AC, and MUC6 were 42+/-27%, 31+/-15%, and 17+/-9%, respectively in GB-chol group and 32+/-22%, 33+/-23%, and 15+/-10%, respectively in GB-pig group (p>0.05). The expression of EGFR was 50% (5/10) in the GB-chol group and 80% (8/10) in the GB-pig group respectively. CONCLUSIONS: There was no difference in the expressions of MUC3, MUC5AC, and MUC6 between the two groups. Further studies are needed to elucidate the role of EGFR in the gallstore formation.