Effects of Helicobacter pylori infection on mucin expression in gastric carcinoma and pericancerous tissues

BACKGROUND: Helicobacter pylori infection is one of the major causes of human gastric carcinoma and can disturb the gastric mucosa barrier. Mucins have not only lubricating and protecting functions, but are also related to signal transduction, turnover of gastric epithelium and carcinogenesis of gastric mucosa. The aim of this study was to investigate the relationship between H. pylori infection and aberrant mucin expression in patients with gastric carcinoma. METHODS: H. pylori infection was diagnosed by the Warthin-Starry staining method. Different kinds of mucins were detected using an immunohistochemical method. RESULTS: Of 46 patients with gastric carcinoma, there were 26 patients who had H. pylori infection (56.5%). Of 21 pericancerous mucosas from the H. pylori-positive patients, 14 had MUC2 expression (66.7%), seven had strong MUC1 expression (+ + +) (33.7%), seven had strong MUC6 expression (+ + +) (33.3%), and five had strong MUC5AC expression (+ + +) (23.8%). In contrast, only six of 18 H. pylori-negative pericancerous mucosas had MUC2 expression (33.3%) (P < 0.05 compared with H. pylori-positive pericancerous mucosas), 12 had strong MUC1 expression (+ + +) in 16 H. pylori-negative pericancerous mucosas (75%) (P < 0.05), 11 had strong MUC6 expression (+ + +) in 16 H. pylori-negative pericancerous mucosas (68.8%) (P < 0.05), and 10 had strong MUC5AC expression (+ + +) in 14 H. pylori-negative pericancerous mucosas (71.4%) (P < 0.01). Of the H. pylori-positive cancerous tissues, 50% (13/26) had MUC1 expression and 38.5% (10/26) had MUC6 expression. In comparison, of the H. pylori-negative cancerous tissues, 80% (16/20) had MUC1 expression (P < 0.05) and 80% (16/20) had MUC6 expression (P < 0.01). CONCLUSIONS: The results indicate that H. pylori infection can alter the expression of some mucin genes in pericancerous mucosa and cancerous tissues of gastric carcinoma, then destroy the gastric mucosa barrier.     

CHANGES IN MUCOSAL PHOSPHOLIPID‐RELATED PROTECTION IN SOME GASTRIC DISEASES

Background: Phospholipids play an important role in gastric mucosal protection. The purpose of the present study was to investigate changes in various phospholipids in the fundic and pyloric gland mucosae of patients with gastric mucosal disease. Methods: One hundred and five patients with superficial gastritis, duodenal ulcer, gastric ulcer or gastric cancer were studied. Patients underwent endoscopy to obtain biopsy specimens from both the fundic and pyloric gland mucosae. The phospholipid contents were measured by high performance liquid chromatography. Results: Total phospholipid level was significantly greater in the fundic gland mucosa than in the pyloric gland mucosa (P = 0.037), and the level in the fundic gland mucosa was high in all four gastric diseases studied. The difference was significant in patients with gastric ulcers (P = 0.0156). Total phospholipid levels were the highest in superficial gastritis, followed by duodenal ulcer, gastric ulcer and gastric cancer. In all four gastric diseases, phosphatidylserine (PS), phosphatidylethanolamine (PE), and phosphatidylcholine (PC) levels were high, while phosphatidylinositol, lysophosphatidylcholine, and sphingomyelin levels were low. The PE and PC levels were higher in the fundic gland mucosa than in the pyloric glandular mucosa, whereas the PS level was higher in the pyloric gland mucosa than in the fundic gland mucosa. Conclusions: The fundic gland mucosa has stronger phospholipid‐related protection than the pyloric gland mucosa, based on the levels of mucosal phospholipids. The main phospholipids for gastric mucosal protection are PC and PE (in the fundic gland mucosa) and PS (in the pyloric gland mucosa). Phospholipid‐related protection is strong in superficial gastritis and duodenal ulcer, but is reduced in the pyloric gland mucosa in patients with gastric ulcers, and in both gastric gland mucosae in patients with gastric cancer.     

Gastric adenocarcinoma of fundic gland type with signet-ring cell carcinoma component: A case report and review of the literature

A depressed lesion was found at a gastric angle of 76-yearold Japanese woman by esophagogastroduodenoscopy. Four years prior, she was diagnosed with a Helicobacter pylori infection but no eradication was performed. The pathological diagnosis of biopsy specimens was signet-ring cell carcinoma. Endoscopic submucosal dissection(ESD) was performed. Histopathological examination of the ESD specimen revealed proliferation of well-differentiated tubular adenocarcinoma mimicking fundic gland cells at the deep layer of the lamina propria mucosae. These tumor cells expressed focally pepsinogen-Ⅰ, diffusely MUC6, and scattered H~+/K~+ ATPase according to immunohistochemistry. Therefore, we diagnosed this tumor as gastric adenocarcinoma of fundic gland type(GA-FG). Adjacent to the GA-FG, proliferation of signet-ring cell carcinoma which diffusely expressed MUC 2 and MUC 5AC was observed. Intestinal metaplasia was focally observed in the surrounding mucosa of the signet-ring cell carcinoma. To the best of our knowledge, this is the first case report of GA-FG with a signet-ring cell carcinoma component. The origin of signet-ring cell carcinoma, i.e., whether it accidentally arose from a non-neoplastic mucosa and coexisted with the GA-FG or dedifferentiated from the GA-FG is unclear at present. We expect the accumulation of similar cases and further analysis to clarify this issue.     

胃底腺黏膜型腺癌一例报道并文献复习

目的探讨胃底腺黏膜型腺癌的临床病理学特征及免疫组化表型。 方法总结山东省立医院西院病理科确诊的1例胃底腺黏膜型腺癌的临床及病理学资料,分析其组织形态学特点及免疫组织化学染色表达,并复习相关文献。 结果老年女性,胃底大弯侧见直径2.0 cm的不规则表浅隆起,中央浅糜烂,行内镜下黏膜剥脱术,肿瘤组织镜下为中-高分化管状腺癌,伴有乳头状腺癌,免疫组化染色小凹上皮分化区域MUC5AC(＋);胃底腺分化区域MUC6(＋)、pepsinogen-I(＋);Ki-67指数约5%。 结论胃底腺黏膜型腺癌是一种新的肿瘤类型,发病率极低,既有胃底腺型腺癌的内镜和病理特征,又有小凹上皮来源腺癌的内镜和病理特征;加强该肿瘤的认识有助于对其正确诊断与治疗。     

Evaluation of multiparameter histologic diagnosis of gastric cancer

AIM: To evaluate multiparameter histologic diagnosis of gastric cancer (GC). METHODS: Expression of the MGa23c7 antigen and the cerbBa22 receptor was detected in specimens of GC by ABC immunohistochemistry. The DNA content of specimens was determined by flow cytometry (FCM). The data of the multiparameter methodology were analyzed statistically. RESULTS: The expression rates of MGa23c7 antigen and cerbBa22 receptor were observed in gastric tubular adenocarcinoma (GTA; 100% and 56% respectively), adenocarcinoma (AC; 58% and 50%) and normal gastric mucosa (NGM; 20% and 33%). The DNA heteroploid rate was 63% (12/19) in GTA, 75% (3/4) in AC and 0% (0/8) in NGM. In detecting GTA with FCM and the ABC method, the histological parameter analysis showed that sensitivity was 82% ± 3%, specificity was 88%, predictive value was 95% ± 4% and accuracy was 84%. Both methods were complementary. CONCLUSION: Multiparameter diagnosis and studies of histomorphology and molecular biology may be a useful approach towards histologic diagnosis of GC.     

H pylori colocalises with MUC5AC in the human stomach

BACKGROUND: The bacterium Helicobacter pylori is able to adhere to and to colonise the human gastric epithelium, yet the primary gene product responsible as a receptor for its adherence has not been identified. AIMS: To investigate the expression of the gastric mucins MUC5AC and MUC6 in the gastric epithelium in relation to H pylori colonisation in order to examine their possible roles in the binding of H pylori. PATIENTS: Seventy two consecutive patients suspected of having H pylori infection. METHODS: MUC5AC, MUC6, and H pylori were detected in single sections of antral biopsy specimens using immunohistochemical triple staining. 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 pits. The expression of both mucins in the epithelium was complementary. In each patient, there was a sharply delineated transition between MUC5AC and MUC6 producing cell populations. In all H pylori positive patients there was a striking colocalization of H pylori and MUC5AC; more than 99% of the bacteria were associated with either extracellular MUC5AC or the apical domain of MUC5AC producing cells. CONCLUSIONS: H pylori is very closely associated with extracellular MUC5AC and epithelial cells that produce MUC5AC. This indicates that MUC5AC, but not MUC6, plays a role in the adhesion of H pylori to the gastric mucosa.     

Cysteamine increases expression and activity of H^＋-K^＋-ATPase of gastric mucosal cells in weaning piglets

AIM: To determine the in vivo and in vivo effects of cysteamine (CS) on expression and activity of H(+)-K(+)-ATPase of gastric mucosal cells in weaning piglets. METHODS: Eighteen litters of newborn Xinhuai piglets were employed in the in vivo experiment and allocated to control and treatment groups. From 12 d of age (D12), piglets in control group were fed basal diet, while the treatment group received basal diet supplemented with 120 mg/kg CS. Piglets were weaned on D35 in both groups. Six piglets from each group (n = 6) were slaughtered on D28 (one week before weaning), D35 (weaning), D36.5, D38, D42, and D45 (36 h, 72 h, one week and 10 d after weaning), respectively. Semi-quantitative RT-PCR was performed to determine the levels of H(+)-K(+)-ATPase mRNA in gastric mucosa. H(+)-K(+)-ATPase activity in gastric mucosa homogenate was also determined. Gastric mucosal epithelial cells from piglets through primary cultures were used to further elucidate the effect of CS on expression and activity of H(+)-K(+)-ATPase in vivo. Cells were treated for 20 h with 0.001, 0.01, and 0.1 mg/mL of CS (n = 4), respectively. The mRNA expression of H(+)-K(+)-ATPase and somatostatin (SS) as well as the H(+)-K(+)-ATPase activity were determined. RESULTS: in vivo, both mRNA expression and activity of H(+)-K(+)-ATPase in gastric mucosa of control group exhibited a trend to increase from D28 to D45, reaching a peak on D45, but did not show significant age differences. Furthermore, neither the mRNA expression nor the activity of H(+)-K(+)-ATPase was affected significantly by weaning. CS increased the mRNA expression of H(+)-K(+)-ATPase by 73%, 53%, 30% and 39% on D28 (P = 0.014), D35 (P = 0.017), D42 (P = 0.013) and D45 (P = 0.046), respectively. In accordance with the mRNA expression, H(+)-K(+)-ATPase activities were significantly higher in treatment group than in control group on D35 (P = 0.043) and D45 (P = 0.040). In vivo, CS exhibited a dose-dependent effect on mRNA expression and activity of H+-K+-ATPase. Both H(+)-K(+)-ATPase mRNA expression and activity in gastric mucosal epithelial cells were significantly elevated after 20 h of exposure to the moderate (H(+)-K(+)-ATPase expression: P=0.03; H(+)-K(+)-ATPase activity: P = 0.014) and high concentrations (H(+)-K(+)-ATPase expression: P=0.017; H(+)-K(+)-ATPase activity: P = 0.022) of CS. Significant increases in SS mRNA expression were observed to accompany the elevation of H(+)-K(+)-ATPase expression and activity induced by the moderate (P = 0.024) and high concentrations (P = 0.022) of CS. Low concentration of CS exerted no effects either on expression and activity of H(+)-K(+)-ATPase or on SS mRNA expression in cultured gastric mucosal epithelial cells. CONCLUSION: No significant changes are observed in mRNA expression and activity of H(+)-K(+)-ATPase in gastric mucosa of piglets around weaning from D28 to D45. CS increases expression and activity of gastric H(+)-K(+)-ATPase in vivo and in vivo. SS is involved in mediating the effect of CS on gastric H(+)-K(+)-ATPase expression and activity in weaning piglets.     

A confirmatory report for the close interaction of Helicobacter pylori with gastric epithelial MUC5AC expression

BACKGROUND: Helicobacter pylori (H. pylori) infection is associated with the development of gastritis and peptic ulcer and is presumed to be a risk factor for low-grade B-cell lymphoma and gastric cancer. H. pylori also causes critical alterations in gastric mucin structure. Our aim was to determine the effect of H. pylori on MUC1, MUC2, and MUC5AC expression. METHODS: Thirty H. pylori-positive and 15 H. pylori-negative antral gastric endoscopic biopsy specimens were evaluated for MUC1, MUC2, and MUC5AC expression with immunohistochemical staining. From the same specimens, we scrutinized the presence of H. pylori infection by hematoxylin and eosin and immunohistochemical staining. RESULTS: In H. pylori infected patients, the expression of MUC5AC was found to be localized to the cells in the superficial epithelium and upper parts of the gastric glands. The number of MUC5AC-expressing cells and the staining intensity of MUC5AC were shown to decrease in patients with H. pylori infection. Histopathology and immunostaining patterns of gastric mucins implied that H. pylori was physically associated with extracellular MUC5AC and MUC5AC-producing cells. H. pylori infection does not significantly affect staining intensity and patterns of MUC1 and MUC2 expressions. MUC1 was not found in dysplastic tissues or intestinal metaplasia areas. MUC5AC was expressed in dysplastic areas, but not in intestinal metaplasia. MUC2 was expressed in both dysplastic and intestinal metaplasia areas. CONCLUSION: H. pylori decreases the amount of MUC5AC expression. With reducing MUC5AC-producing cells and MUC5AC mucin, H. pylori may potentially cause significant alterations of the structure and function of gastric mucins. H. pylori-dependent inhibition of mucin synthesis deserves more investigations to clarify the role of H. pylori and gastric MUC5AC interaction.     

黏蛋白在胃癌的诊断和预后评估中的作用

黏蛋白是由特殊的上皮细胞分泌的大分子量糖蛋白。多项研究显示黏蛋白在不同胃黏膜病变尤其在胃腺癌的不同类型中存在不同的表达:MUC1、MUC5AC、MUC6在正常胃黏膜中呈强阳性表达而MUC2则不表达。在正常胃黏膜向肠上皮化生、胃癌演进过程中,MUC1、MUC5AC、MUC6表达呈下调趋势而MUC2表达上调。此文就胃腺癌的不同类型及其发展,黏蛋白在不同胃黏膜病变中的表达及其在胃腺癌的诊断和预后评估中的作用等做一概述。     

Does ampullary carcinoma arise from distended glands in the papilla of Vater?

Background/Purpose

Glands near the surface of the papilla of Vater may become distended with mucus and become hyperplastic; that is, become distended. In this study, we tried to clarify carcinogenesis in these distended glands.

Methods

Twenty-nine pancreatoduodenectomized nontumorous duodenal papilla specimens from carcinoma of the pancreas and bile duct and 34 resected ampullary carcinoma specimens were studied histopathologically and immunohistochemically, using cytokeratins and mucin immunohistochemical features/phenotypes.

Results

Distended glands were found in 11 of the 29 pancreatoduodenectomized specimens. These glands were immunopositive for cytokeratin (CK) 7 and MUC-5AC Glycoprotein (MUC5AC), but not for CK20, while the intrapapillary portion was CK7-positive and CK20-negative, but mostly negative for MUC5AC. Immunopositivity for CK7, CK20, and MUC5AC was found in 25, 21, and 18 of the 34 specimens of ampullary carcinoma, respectively. In 23 of the 34 specimens, immunoreactivity for MUC5AC and that for CK7 was coincident, that is, when the former was immunopositive, so was the latter, and vice versa, while in 25 of the 34 specimens, immunoreactivity for MUC5AC was opposite to that for CK20. Among the 23 cases in which immunoreactivity for MUC5AC and CK7 was coincident, 10 were MUC5AC+, CK7+, CK20? and 7 were MUC5AC?, CK7?, CK20+, suggestive of disease arising from the pancreaticobiliary mucosa or the distended glands in the former and disease arising from the duodenal mucosa in the latter. In MUC5AC+ cases, other than the 10 cases of MUC5AC+, CK7+, CK20?, 6 were double-positive and 1 was double-negative for CK7 and CK20, and 1 was CK20-positive, and at least 1 case showing double-negativity for CK7 and CK20 was suggestive of disease arising from the distended glands.

Conclusions

Although most ampullary carcinomas arise from the duodenal mucosa or intra-ampullary mucosa, both CK7-positive and MUC5AC-positive or only MUC5ACpositive ampullary carcinomas may arise from the distended glands.

     

PDX1 homeobox protein expression in pseudopyloric glands and gastric carcinomas

BACKGROUND AND AIMS: Although it has been reported that intestinal metaplasia implicated in gastric carcinogenesis is induced by the ParaHox gene CDX2, it is unclear which genes are responsible for the formation of pseudopyloric glands and whether they play a role in gastric carcinogenesis. Pancreatic-duodenal homeobox 1 (PDX1) is also a ParaHox gene which contributes to the genesis and development of the pancreas, duodenum, and antrum. To clarify its significance for the formation of pseudopyloric glands and gastric carcinogenesis, we investigated expression of PDX1 and mucin in gastric carcinomas and surrounding mucosa. METHODS: Gastric carcinoma tissues from 95 patients were used for immunohistochemical analyses of PDX1, and mucins MUC6 and MUC5AC. RESULTS: PDX1 was found to be frequently expressed in pseudopyloric glands and intestinal metaplasia. MUC6 was more abundant than MUC5AC in pseudopyloric glands while higher levels of MUC5AC than MUC6 were evident in intestinal metaplasia. The frequency of PDX1 positive reactivity was higher in differentiated type carcinomas (39/43, 90.7%) and T1 carcinomas (42/43, 97.7%) than in undifferentiated type (33/52, 63.5%) and T2-4 (30/52, 57.7%) carcinomas. PDX1 and MUC6 double positive expression was observed in carcinomas, respectively, including the corpus, and also correlated with histological type and depth of invasion. In contrast, no link was apparent between PDX1 and MUC5AC double positive reactivity and histological type. CONCLUSION: Our study suggests that PDX1 plays an important role in the development of pseudopyloric glands, and that pseudopyloric glands may reflect a condition associated with gastric carcinogenesis.     

GASTRIC ADENOCARCINOMA OF FUNDIC GLAND TYPE (CHIEF CELL PREDOMINANT TYPE) TREATED WITH ENDOSCOPIC ASPIRATION MUCOSECTOMY

Upper endoscopy screening in an asymptomatic 56‐year‐old man showed a small, yellowish elevated lesion with a central depression on the posterior wall in the gastric cardia. Biopsy specimens from this lesion were suspicious of carcinoid tumor. We suspected this lesion to be a sporadic gastric carcinoid tumor with a diameter of 5 mm, limited to the mucosal layer. We then performed an endoscopic aspiration mucosectomy with a cap‐fitted endoscope. Microscopically, the lesion obtained from the resected specimen was minimally invasive to the submucosa and showed highly differentiated columnar cells in irregularly anastomosing glands. Immunohistology was positive for pepsinogen‐I, and MUC6, partially positive for H⁺/K⁺‐ATPase, and negative for MUC5AC. In addition, it was positive for synaptophysin and CD56, and negative for chromogranin A. We finally diagnosed the patient as having gastric adenocarcinoma of fundic gland type (chief cell predominant type) with minimal invasion (100 µm) to the submucosa. Surveillance endoscopy with biopsy specimens and abdominal computed tomography at 1 year revealed no evidence of tumor recurrence. We herein report this rare case of gastric adenocarcinoma of fundic gland type (chief cell predominant type).     

Phosphatidylcholine and lysophosphatidylcholine in intestinal mucus of ulcerative colitis patients. A quantitative approach by nanoElectrospray-tandem mass spectrometry

BACKGROUND: A defective mucus composition represents a key pathogenetic factor for intestinal injury. Phosphatidylcholine (PC) is an essential component contributing to formation of a hydrophobic mucus layer. For evaluation of PC in the pathogenesis of inflammatory bowel disease, the concentration and composition of PC in the rectal mucus of patients with ulcerative colitis was determined. Electrospray ionization (ESI) tandem mass spectrometry (MS/MS) allows quantification of PC species and enables analysis of crude extracts. METHODS: Lipid extracts of material obtained by light scrapings of the intestinal lumen were analysed quantitatively by nanoESI MS/MS with synthetic internal PC and lysophosphatidylcholine (LPC) standards. PC and LPC species from rectoscopically acquired mucus aliquots of patients with ulcerative colitis were compared to Crohn disease and control subjects. RESULTS: Patients with inactive ulcerative colitis showed significantly less PC and LPC (median 346 [IQR: 230-405] pmol total PC/mg dry weight) in rectal mucus compared to Crohn disease (median 126 [IQR: 465-1941] pmol total PC/mg dry weight) and control subjects (median 1285 [IQR: 850-1639] pmol total PC/mg dry weight) (P < 0.05). The molecular species of PC and LPC were not significantly different between the groups. The most abundant species were PC 16:0/18:1; PC 16:0/18:2; PC 18:0/18:1; PC 18:0/18:2; LPC 16:0; and LPC 18:0. CONCLUSION: NanoESI MS/MS is a suitable tool for analysing and quantifying small amounts of PC in human mucus. Patients with ulcerative colitis have significant less PC in their intestinal mucus despite a comparable PC molecular species composition pattern. This suggests that a low amount of protective mucus PC is a characteristic feature in ulcerative colitis and explains an increased susceptibility to luminal contents.     

Endoscopic Characteristics of Gastric Polyps and Their Background Mucosa on the Gastric Body

Abstract: We investigated the endoscopic and histopathological characteristics of 112 gastric polyps on the gastric body. According to the histopathological findings of the glands in the biopsy specimens, we classified the polyps into 6 categories; dense fundic gland type (group A), sparse fundic gland type (B), mixed fundic and pyloric gland type (C), pyloric gland type (D), complete atrophic gland type (E) and others (F). The grade of atrophic gastritis was defined by the fundic-pyloric border type of the stomach, and was found to change from mild to severe respectively in groups A to E. The gastric area type of background fundic gland mucosa also changed from F₀ to F₃ in parallel with the order of the groups A to E. Thirty-five of the 36 polyps in group A, all 19 in group B, 2 out of 3 in group C, 1 of 4 in group D, and the 1 in group E were located on the dye-endoscopically defined fundic gland mucosal area. The gland type of biopsy specimens which were obtained from the mucosa adjacent to the polyps changed from fundic to fundic-pyloric and to pyloric type in groups A to E respectively. In conclusion, the histopathological findings of polyps on the gastric body reflect the background mucosa, and in particular the extent of the atrophic change of the stomach. The majority of polyps, either fundic gland polyps (groups A and B) or hyperplastic polyps (groups C, D and E), on the gastric body were found to be the same gland type as their respective background mucosa. They thus seem to fall into the same category as hyperplastic polyps of background mucosal origin but are not the same as a hamartomatous polyp.     

“湿”证与幽门螺旋杆菌感染的相关性及对胃黏液蛋白MUCA5AC、MUC6、MUC1表达的影响

[目的]探索"湿"证与幽门螺旋杆菌(HP)感染的相关性及对胃黏膜屏障中胃黏液蛋白MUCA5AC、MUC6、MUC1表达的影响。[方法]以随机数字表法将研究对象分为观察组(湿证)和对照组(健康体检人群),每组各80例,研究与HP感染的相关性,并进一步探索2组胃黏膜中MUCA5AC、MUC6、MUC1因子的表达情况。[结果]湿证组中HP阳性率明显高于对照组,2组之间差异有统计学意义(P<0.05)。湿证与HP感染呈正相关(r=0.681,P<0.01)。观察组胃黏膜中MUCA5AC、MUC6、MUC1因子表达明显低于对照组(P<0.05)。[结论]湿邪能降低胃黏膜屏障中黏液蛋白的表达,破坏胃黏膜屏障,可能是HP感染或复发的关键病理因素。     

Mucin gene expression in Barrett's oesophagus: an in situ hybridisation and immunohistochemical study

BACKGROUND AND AIMS: Mucin genes are expressed in a site specific manner throughout the gastrointestinal tract. Little is known about the expression pattern in the oesophagus. In this study we have investigated MUC gene expression in both the normal oesophagus and specialised intestinal metaplasia (Barrett's oesophagus). PATIENTS: Archived paraffin embedded material from eight specimens of normal oesophagus, 18 Barrett's oesophagus, eight gastric metaplasia, six high grade dysplasia, and six cases of adenocarcinoma were examined for expression of the mucin genes MUC1-6. METHODS: Mucin mRNA was detected by in situ hybridisation using [(35)S] dATP labelled oligonucleotide probes. Mucin core protein was detected by immunohistochemistry. RESULTS: Normal oesophagus expressed MUC5B in the submucosal glands and MUC1 and MUC4 in the stratified squamous epithelium. Barrett's oesophagus strongly expressed MUC5AC and MUC3 in the superficial columnar epithelium, MUC2 in the goblet cells, and MUC6 in the glands. In high grade dysplasia and adenocarcinoma there was downregulation of MUC2, MUC3, MUC5AC, and MUC6, but upregulation of MUC1 and MUC4 in half of the specimens examined. CONCLUSIONS: Normal oesophagus and Barrett's oesophagus have a novel pattern of mucin gene expression. Barrett's oesophagus expressed the mucins associated with normal gastric epithelium and normal intestinal epithelium. While most mucin genes were downregulated in severely dysplastic and neoplastic tissues, there was upregulation of the membrane bound mucins MUC1 and MUC4. This may prove useful in detecting early signs of progression to adenocarcinoma of the oesophagus.     

Prognostic Significance of Mucin Expression in Gastric Carcinoma

In patients with gastric carcinomas, the role of the alteration of mucin expression in overall survival has been a matter of some speculation, but few studies have been reported. The aim of our study was to determine the relationship between MUC1, MUC2, and MUC5AC expression and patient survival, with a secondary aim designed to investigate the alteration of MUC expression within various clinicopathologic parameters. Forty-four specimens from gastric carcinoma patients were immunohistochemically evaluated using the monoclonal antibodies for MUC1 (EMA, clone E29), MUC2 (CCP58), and MUC5AC (human gastric mucin, clone 45M1). MUC1 expression increased in gastric carcinoma. MUC1 positivity was determined to be statistically significant, with poor clinicopathological parameters and decreased long-term survival. MUC5AC expression decreased in gastric carcinoma. In addition, patients with MUC5AC-positive tumors also had poor clinicopathological parameters and showed shorter survival than those with MUC5AC-negative tumors. MUC2 expression was not significantly associated with patient survival. We confirmed that the expression of mucins is associated with characteristics of differentiation in gastric carcinoma. Poor patient outcomes were seen in gastric carcinomas with MUC1 mucin expression and MUC5AC positivity.