Prognostic significance of mucins in colorectal cancer with different DNA mismatch-repair status
Alessandro Lugli 1, Inti Zlobec 1, Kristi Baker 1, Parham Minoo 1, Luigi Tornillo 2, Luigi Terracciano 2 and Jeremy Jass 3*
1 Department of Pathology McGill University Montreal, Canada
2 Institute of Pathology University Hospital Basel, Switzerland
3 Department of Pathology McGill University, Canada
* To whom correspondence should be addressed. E-mail: jeremy.jass{at}mcgill.ca.
Accepted 19 May 2006
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Abstract |
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Background: MUC1 expression and downregulation of MUC2 are associated with adverse prognosis in colorectal cancer (CRC), but their prognostic significance with respect to differing DNA mismatch repair (MMR) status is poorly understood.
Objective: To determine the prognostic significance of MUC1 and MUC2 in CRC with different MMR status.
Methods: Using the tissue microarray (TMA) technique a series of 1420 unselected, non-consecutive CRC resections were subdivided into three groups: (1) MMR-proficient, (2) MLH1-negative, and (3) presumed HNPCC. Immunohistochemical analysis of MUC1 and MUC2 expression (>0%) and loss (0%) was performed and the results were correlated with clinico-pathological parameters.
Results: In MMR-proficient CRC MUC1 expression was more frequently found in tumours with higher T stage (p=0.004) and higher tumour grade (p=0.041) and loss of MUC2 was associated with higher T stage (p=0.028), N 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 presence of lymph node metastasis (p=0.028) and worse survival (p=0.015) but there was no association between MUC1 expression and clinico-pathological features. In presumed HNPCC MUC1 expression and MUC2 loss were not associated with clinico-pathological parameters.
Conclusions: Mucins have a prognostic significance in sporadic, 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 only in MMR-proficient CRC.
Key Words:
colorectal cancer, immunohistochemistry, mismatch repair status, mucins, tissue-microarray
