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

Abstract

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.

• Authors: A Lugli, I Zlobec, K Baker, P Minoo, L Tornillo, L Terracciano, J R Jass
• Journal: Journal of clinical pathology (J Clin Pathol) Vol. 60 Issue 5 Pg. 534-9 (May 2007) ISSN: 0021-9746 [Print] England
• PMID: 16816167 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, Neoplasm
• Biomarkers, Tumor
• DNA, Neoplasm
• MUC1 protein, human
• MUC2 protein, human
• Mucin-1
• Mucin-2
• Mucins
• Neoplasm Proteins

Topics

• Adult
• Aged
• Aged, 80 and over
• Antigens, Neoplasm (metabolism)
• Biomarkers, Tumor (metabolism)
• Colorectal Neoplasms (genetics, metabolism, pathology)
• DNA Mismatch Repair
• DNA, Neoplasm (genetics)
• Disease Progression
• Female
• Humans
• Immunoenzyme Techniques
• Male
• Middle Aged
• Mucin-1
• Mucin-2
• Mucins (metabolism)
• Neoplasm Invasiveness
• Neoplasm Proteins (metabolism)
• Neoplasm Staging
• Prognosis
• Protein Array Analysis (methods)
• Survival Analysis