ORIGINAL ARTICLE

Prognostic significance of mucins in colorectal cancer with different DNA mismatch-repair status

A Lugli^1,2, I Zlobec¹, K Baker¹, P Minoo¹, L Tornillo², L Terracciano² and J R Jass¹

¹ Department of Pathology, McGill University, Duff Medical Building, Montreal, Quebec, Canada
² Institute of Pathology, University Hospital of Basel, Basel, Switzerland

Correspondence to:
Correspondence to:
Professor J R Jass
Department of Pathology, McGill University, Duff Medical Building, 3775 University Street, Montreal H3A 2B4, Quebec, Canada; jeremy.jass{at}mcgill.ca

Background: Expression of mucin antigen MUC1 and down regulation of MUC2 are associated with adverse prognosis in colorectal cancer (CRC), but their prognostic significance with respect to differing DNA mis- match repair (MMR) status is poorly understood.

Objective: To determine the prognostic significance of MUC1 and MUC2 in CRC with different MMR statuses.

Methods: Using the tissue microarray (TMA) technique, a series of 1420 unselected, non-consecutive CRC resections was subdivided into three groups: (1) MMR-proficient; (2) MLH1-negative; and (3) presumed hereditary non-polyposis colon cancer (HNPCC). Immunohistochemical analysis of MUC1 and MUC2 expression (>0%) and loss (0%) was performed, and the results were correlated with clinicopathological parameters.

Results: In MMR-proficient CRC, MUC1 expression was more frequently found in tumours with higher tumour stage (p = 0.004) and higher tumour grade (p = 0.041) and loss of MUC2 was associated with higher tumour stage (p = 0.028), node stage (p = 0.001), presence of vascular invasion (p = 0.028) and worse survival (p = 0.034). In MLH1-negative CRC, MUC2 loss was associated with the presence of lymph node metastasis (p = 0.028) and worse survival (p = 0.015), but there was no association between MUC1 expression and clinicopathological features. In presumed HNPCC, MUC1 expression and MUC2 loss were not associated with clinicopathological parameters.

Conclusions: Mucins have a prognostic significance in sporadic CRC, but not in hereditary CRC. Loss of MUC2 is an adverse prognostic factor in MMR-proficient and MLH1-negative CRC, whereas MUC1 expression is associated with tumour progression in MMR-proficient CRC only.

Abbreviations: CRC, colorectal cancer; HNPCC, hereditary non-polyposis colon cancer; MMR, mismatch repair; MUC, mucin; MSI-H, microsatellite instability-high; TMA, tissue microarray

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