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

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, therefor...

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Published in:Modern pathology 2013-12, Vol.26 (12), p.1642-1656
Main Authors: 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
Format: Article
Language:English
Subjects:
631/208/176/1988
692/420/2489/68
692/699/67/1504/1885
Adult
Aged
Aged, 80 and over
Biomarkers, Tumor - analysis
Carcinoma - genetics
Carcinoma - metabolism
CDX2 Transcription Factor
Cohort analysis
Collaboration
Colorectal cancer
Colorectal Neoplasms - genetics
Colorectal Neoplasms - metabolism
CpG Islands - genetics
DNA Methylation - genetics
Epidemiology
Female
Gene expression
Gene Silencing
Genotype & phenotype
Histopathology
Homeodomain Proteins - biosynthesis
Humans
Immunohistochemistry
Laboratory Medicine
Male
Medical research
Medicine
Medicine & Public Health
Microsatellite Instability
Middle Aged
Mucin 5AC - analysis
Mucin 5AC - biosynthesis
Mucin-2 - analysis
Mucin-2 - biosynthesis
Mucin-5B - analysis
Mucin-5B - biosynthesis
Mucin-6 - analysis
Mucin-6 - biosynthesis
Mucins - analysis
Mucins - biosynthesis
Mutation
original-article
Pathology
Phenotype
Polymerase Chain Reaction
Protein expression
Proteins
Proto-Oncogene Proteins B-raf - genetics
Signal transduction
Tumors
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Summary: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
ISSN:0893-3952
1530-0285
DOI:10.1038/modpathol.2013.101