title: 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.affiliation: Department of Pathology, McGill University, Duff Medical Building, Montreal, Quebec, Canada.
authors.forename: A
authors.initials: A
authors.lastname: Lugli
authors.forename: I
authors.initials: I
authors.lastname: Zlobec
authors.forename: K
authors.initials: K
authors.lastname: Baker
authors.forename: P
authors.initials: P
authors.lastname: Minoo
authors.forename: L
authors.initials: L
authors.lastname: Tornillo
authors.forename: L
authors.initials: L
authors.lastname: Terracciano
authors.forename: J R
authors.initials: JR
authors.lastname: Jass
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000378:metabolism*; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D053843:DNA Mismatch Repair; D004273:DNA, Neoplasm / Q000235:genetics; D018450:Disease Progression; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D018396:Mucin-1; D055262:Mucin-2; D009077:Mucins / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000378:metabolism; D009367:Neoplasm Staging; D011379:Prognosis; D040081:Protein Array Analysis / Q000379:methods; D016019:Survival Analysis
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; C060192:MUC1 protein, human; C524625:MUC2 protein, human; D018396:Mucin-1; D055262:Mucin-2; D009077:Mucins; D009363:Neoplasm Proteins