Lynch syndrome-associated breast cancers do not overexpress chromosome 11-encoded mucins

M.D. Walsh, M.C. Cummings, S.A. Pearson, M. Clendenning, R.J. Walters, B. Nagler, J.L. Hopper, M.A. Jenkins, G.K. Suthers, Jack Goldblatt, K. Tucker, M.R. Gattas, J.L. Arnold, S. Parry, F.A. Macrae, M.A. Mcguckin, J.P. Young, D.D. Buchanan

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    Abstract

    Mismatch repair-deficient breast cancers may be identified in Lynch syndrome mutation carriers, and have clinicopathological features in common with mismatch repair-deficient colorectal and endometrial cancers such as tumour-infiltrating lymphocytes and poor differentiation. Mismatch repair-deficient colorectal cancers frequently show mucinous differentiation associated with upregulation of chromosome 11 mucins. The aim of this study was to compare the protein expression of these mucins in mismatch repair-deficient and -proficient breast cancers. Cases of breast cancer (n=100) were identified from families where (1) both breast and colon cancer co-occurred and (2) families met either modified Amsterdam criteria or had at least one early-onset (<50 years) colorectal cancer. Tumour sections were stained for the epithelial mucins, MUC2, MUC5AC, MUC5B and MUC6, and the homeobox protein CDX2, a regulator of MUC2 expression. In all, 16 mismatch repair-deficient Lynch syndrome breast cancers and 84 non-Lynch breast cancers were assessed for altered mucin expression. No significant difference in the expression of MUC2, MUC5AC or MUC6 was observed between the mismatch repair-deficient and mismatch repair-proficient breast cancers; however, there was a trend for mismatch repair-deficient tumours to express high levels of MUC5B less frequently (P=0.07, OR=0.2 (0.0–1.0)). Co-expression of two or more gel-forming mucins was common. Ectopic expression of CDX2 was associated with expression of MUC2 (P=0.035, OR=8.7 (1.3–58.4)). Mismatch repair-deficient breast cancers do not show differential expression of the mucins genes on chromosome 11 when compared with mismatch repair-proficient breast cancers, in contrast with mismatch repair-deficient colorectal and endometrial cancers, which frequently have increased mucin protein expression when compared with their mismatch repair-proficient counterparts. In addition, ectopic CDX2 expression is positively associated with de novo MUC2 expression.
    Original languageEnglish
    Pages (from-to)944-954
    JournalModern Pathology
    Volume26
    Issue number7
    Early online date1 Feb 2013
    DOIs
    Publication statusPublished - Jul 2013

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    Walsh, M. D., Cummings, M. C., Pearson, S. A., Clendenning, M., Walters, R. J., Nagler, B., ... Buchanan, D. D. (2013). Lynch syndrome-associated breast cancers do not overexpress chromosome 11-encoded mucins. Modern Pathology, 26(7), 944-954. https://doi.org/10.1038/modpathol.2012.232