Immunohistochemical study of MUC5AC expression in human gastric carcinomas using a novel monoclonal antibody

Reis, Celso A.; David, Leonor; Nielsen, Peter Aadal; Clausen, Henrik; Mirgorodskaya, Katja; Roepstorff, Peter; Sobrinho‐Simöes, Manuel

doi:10.1002/(sici)1097-0215(19970220)74:1<112::aid-ijc19>3.0.co;2-h

Cited by 173 publications

(108 citation statements)

References 28 publications

(19 reference statements)

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“…MUC5AC was thought to be gastric mucin and expressed higher in early stage of cancers than in the advanced stage [18] . MUC5AC rarely expressed in mucinous carcinoma except in one case.…”

Section: Discussionmentioning

confidence: 99%

Expression of mucins and E-cadherin in gastric carcinoma and their clinical significance

Zhang

Zhang²,

Zhao³

et al. 2004

WJG

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AIM:To investigate the expression of three types of mucin (MUC1, MUC2, MUC5AC) and E-cadherin in human gastric carcinomas and their clinical significance. METHODS:Ninety-four gastric cancer specimens were classified according to WHO criteria and detected by immunohistochemical assay of expression of mucins and E-cadherin. RESULTS:The positive expression rates of MUC1, MUC2, MUC5AC and E-cadherin were 82% (77/94), 84% (79/94), 40% (38/94) and 56% (53/94) respectively. MUC1 expression was significantly correlated with the types of cancer (the positive rates of MUC1 in well and moderately differentiated tubular adenocarcinoma, poorly differentiated adenocarcinoma, signet-ring cell carcinoma and mucinous carcinoma were 91%, 87%, 71%, 71%, respectively, P<0.05), age of patients (the positive rates of it among the people who are younger than 40 years, between 40-60 years and over 60 year were 74%, 81%, 89%, P<0.05), lymph nodes involvement (the positive rates in the non-interfered group and the interfered group were 78%, 85%, P<0.05) and tumor size (the positive rates in the tumors with the size less than 3 cm, 3-6 cm and larger than 6 cm were 69%, 92%, 69%, P<0.05); MUC2 expression was significantly associated with types of cancers and had the strongest expression in mucinous carcinomas (the positive rates of MUC2 in well and moderately differentiated tubular adenocarcinoma, poorly differentiated adenocarcinoma, signet-ring cell carcinoma and mucinous carcinoma were 94%, 70%, 81%, 100%, P<0.05), but it had no obvious relation to age, gender, tumor location, lymph nodes involvement, depth of invasion and metastasis to extra-gastric organs (P>0.05); MUC5AC expression was not related to any of the characteristics investigated except that it had relation to gender, whereas MUC5AC showed the tendency to higher expression in less invasive lesions and lower expression in advanced stage cancers (P>0.05); No significant difference was found for E-cadherin expression. There were strong positive relationships between the expression of MUC1 and E-cadherin, MUC2 and E-cadherin, MUC1 and MUC2 (R = 0.33, R = 0.22, R = 0.32, respectively, P<0.05). According to the COX proportional hazards model, older patients, involvement of lymph nodes, different types of gastric cancer and MUC2 expression were significantly associated with poorer outcome of gastric carcinoma patients (β = 0.08, β = 3.94, β = 1.33, β = 0.75, respectively, P<0.05).CONCLUSION: MUC1 and MUC2 are good markers of different types of gastric cancer. MUC2 is especially a good marker of mucinous carcinoma. MUC1, MUC2 may interfere with the function of E-cadherin in gastric carcinomas, and have synergic effect on progression of gastric cancers.Zhang HK, Zhang QM, Zhao TH, Li YY, Yi YF. Expression of mucins and E-cadherin in gastric carcinoma and their clinical significance.

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“…MUC5AC was thought to be gastric mucin and expressed higher in early stage of cancers than in the advanced stage [18] . MUC5AC rarely expressed in mucinous carcinoma except in one case.…”

Section: Discussionmentioning

confidence: 99%

Expression of mucins and E-cadherin in gastric carcinoma and their clinical significance

Zhang

Zhang²,

Zhao³

et al. 2004

WJG

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“…11 Gastric and intestinal mucosas are protected by a mucus layer of high molecular weight glycoproteins synthesized by normal epithelial cells in a cell-and tissue-specific pattern. 12,13 MUC5AC and MUC6 are the protein cores of gastric mucus, foveolar and mucopeptic, respectively. MUC2 is the protein constituent of the intestinal mucus.…”

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confidence: 99%

Chromosomal analysis of Barrett's cells: demonstration of instability and detection of the metaplastic lineage involved

et al. 2007

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Barrett's esophagus is lined by columnar and goblets cells with gastric and intestinal characteristics. Despite the association between goblet elements and malignancy, it was not demonstrated that other columnar cells lineages are not related to neoplasia. Chromosomal abnormalities were described in metaplasia adjacent to Barrett's neoplasia, but it is unknown which metaplastic lineages are involved. This work assessed the frequency and the type of chromosomal abnormalities in Barrett's esophagus without neoplasia and performed the identification of the metaplastic cells carrying chromosomal gains. Barrett's esophagus biopsies were collected and processed for short-term cell culture and cytogenetic analysis. Combined immunofluorescence/ fluorescence in situ hybridization was performed in cases exhibiting chromosomal gains by using antisera against intestinal (MUC2) and gastric (MUC5AC and MUC6) apomucins and chromosome pericentromeric alpha satellite DNA probes for the chromosomes involved. Each case was scored for the number of spots (0, 1, 2, 42) in 200 nonoverlapping nuclei. Columnar and goblet cells were separately assessed. Short-term cell cultures were achieved in 40/60 cases (67%). There were clonal abnormalities in 27/40 cases (68%) and tetraploid (4n) clones in 10/40 (25%). Structural alterations were detected in 14/40 (35%) with recurrent breakpoints at 1q21, 15q15 and 15q22. Numerical changes (trisomies 7 and 18 and loss of Y) occurred in 16/40 (40%). Gains of chromosomes 7 and 18 were more frequent in columnar than in goblet cells (9.8% vs 0.7% (Po0.05)) and (7.9 vs 1.9% (Po0.05)) respectively. These alterations were detected in cells exhibiting gastric as well as intestinal features and were more frequent in cells without apomucin production. Conclusions: (1) chromosomal instability is a common finding in Barrett's esophagus without neoplasia. (2) The two metaplastic populations are committed, chromosomal gains being more frequent in columnar nongoblet than in goblet cells. (3) The two metaplastic phenotypes, gastric and intestinal, are equally involved.

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“…1 In normal gastric epithelium, MUC5AC is highly expressed in foveolar cells of the body and the antrum, [2][3][4] while MUC6 is expressed in the pyloric glands of the antrum. 5,6 Other mucins are not generally expressed in normal gastric mucosa, although MUC2 is often focally expressed in some gastric epithelium.…”

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confidence: 99%

Subcellular localization of ATBF1 regulates MUC5AC transcription in gastric cancer

Mori

Kataoka

Miura

et al. 2007

Intl Journal of Cancer

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Human gastric epithelium has a unique mucin gene expression pattern, which becomes markedly altered in gastrointestinal disorder. This alteration in mucin expression, including the mucin MUC5AC, may be related to the development and prognosis of gastric cancers, and MUC5AC-positive gastric cancer has been reported to be poor prognosis. However, the molecular mechanism of MUC5AC transcriptional regulation has not been fully elucidated. AT motif-binding factor 1 (ATBF1) is a homeotic transcriptional regulatory factor recently identified as a tumor suppressor gene, and its subcellular localization suggests a link to cell proliferation and differentiation. We investigated the mechanism of MUC5AC transcriptional regulation by ATBF1. In 123 gastric cancer lesions, ATBF1 expressed in the nucleus significantly suppressed MUC5AC expression, as determined by immunohistochemistry. In addition, analysis of the MUC5AC promoter region revealed an AT motif-like element. This element was found to be essential for ATBF1 suppression of MUC5AC promoter activity as shown in a dual luciferase-reporter assay. Over-expressed ATBF1 also significantly suppressed endogenous MUC5AC protein expression in gastric cancer cells. Chromatin immunoprecipitation demonstrated that ATBF1 binds to the AT motif-like element in the MUC5AC promoter. These results indicate that ATBF1 in the nucleus negatively regulates the MUC5AC gene in gastric cancer by binding to an AT motif-like element in the MUC5AC promoter. ' 2007 Wiley-Liss, Inc.

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Immunohistochemical study of MUC5AC expression in human gastric carcinomas using a novel monoclonal antibody

Cited by 173 publications

References 28 publications

Expression of mucins and E-cadherin in gastric carcinoma and their clinical significance

Expression of mucins and E-cadherin in gastric carcinoma and their clinical significance

Chromosomal analysis of Barrett's cells: demonstration of instability and detection of the metaplastic lineage involved

Subcellular localization of ATBF1 regulates MUC5AC transcription in gastric cancer

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