Expression of MUC2, MUC5AC, MUC5B, and MUC6 mucins in colorectal cancers and their association with the CpG island methylator phenotype

Walsh, Michael D., Clendenning, Mark, Williamson, Elizabeth, Pearson, Sally-Ann, Walters, Rhiannon J., Nagler, Belinda, Packenas, David, Win, Aung K., Hopper, John L., Jenkins, Mark A., Haydon, Andrew M., Rosty, Christophe, English, Dallas R., Giles, Graham G., McGuckin, Michael A., Young, Joanne P. and Buchanan, Daniel D. (2013) Expression of MUC2, MUC5AC, MUC5B, and MUC6 mucins in colorectal cancers and their association with the CpG island methylator phenotype. Modern Pathology, 26 12: 1642-1656. doi:10.1038/modpathol.2013.101

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Author Walsh, Michael D.
Clendenning, Mark
Williamson, Elizabeth
Pearson, Sally-Ann
Walters, Rhiannon J.
Nagler, Belinda
Packenas, David
Win, Aung K.
Hopper, John L.
Jenkins, Mark A.
Haydon, Andrew M.
Rosty, Christophe
English, Dallas R.
Giles, Graham G.
McGuckin, Michael A.
Young, Joanne P.
Buchanan, Daniel D.
Title Expression of MUC2, MUC5AC, MUC5B, and MUC6 mucins in colorectal cancers and their association with the CpG island methylator phenotype
Journal name Modern Pathology   Check publisher's open access policy
ISSN 0893-3952
Publication date 2013-01-01
Year available 2013
Sub-type Article (original research)
DOI 10.1038/modpathol.2013.101
Open Access Status DOI
Volume 26
Issue 12
Start page 1642
End page 1656
Total pages 15
Place of publication London, United Kingdom
Publisher Nature Publishing Group
Language eng
Subject 2734 Pathology and Forensic Medicine
Abstract Mucinous differentiation is associated with both CpG island methylator phenotype and microsatellite instability in colorectal cancer. The mucinous phenotype derives from abundant expression of the colonic goblet cell mucin, MUC2, and de novo expression of gastric foveolar mucin, MUC5AC. We, therefore, investigated the protein expression levels of MUC2 and MUC5AC, as well as MUC5B and MUC6, in molecular subtypes of colorectal cancer. Seven-hundred and twenty-two incident colorectal carcinomas occurring in 702 participants of the Melbourne Collaborative Cohort Study were characterized for methylator status, MLH1 methylation, somatic BRAF and KRAS mutations, microsatellite-instability status, MLH1, MSH2, MSH6, and PMS2 mismatch repair, and p53 protein expression, and their histopathology was reviewed. Protein expression levels of MUC2, MUC5AC, MUC5B, MUC6, and the putative mucin regulator CDX2 were compared with molecular and clinicopathological features of colorectal cancers using odds ratios and corresponding 95% confidence intervals. MUC2 overexpression (>25% positive tumor cells) was observed in 33% colorectal cancers, MUC5B expression in 53%, and de novo MUC5AC and MUC6 expression in 50% and 39%, respectively. Co-expression of two or more of the mucins was commonly observed. Expression of MUC2, MUC5AC and MUC6 was strongly associated with features associated with tumorigenesis via the serrated neoplasia pathway, including methylator positivity, somatic BRAF p.V600E mutation, and mismatch repair deficiency, as well as proximal location, poor differentiation, lymphocytic response, and increased T stage (all P<0.001). Overexpression was observed in tumors with and without mucinous differentiation. There were inverse associations between expression of all four mucins and p53 overexpression. CDX2 expression was inversely associated with MUC2, MUC5AC and MUC6 expression. Our results suggest that, in methylator-positive tumors, mucin genes on chromosome 11p15.5 region undergo increased expression via mechanisms other than direct regulation by CDX2.
Keyword Colorectal cancers
Biological heterogeneity
Neoplastic Progression
Q-Index Code C1
Q-Index Status Confirmed Code
Grant ID APP209057
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: UQ Centre for Clinical Research Publications
Official 2014 Collection
School of Medicine Publications
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Citation counts: TR Web of Science Citation Count  Cited 39 times in Thomson Reuters Web of Science Article | Citations
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