Author: Nat Pernick, M.D. (see Authors page)

Revised: 11 November 2015, last major update June 2005

Copyright: (c) 2002-2015,, Inc.

PubMed Search: Mucins [title]

Definition / General
  • Also called mucopolysaccharides; major glycoprotein components of mucus under normal circumstances
  • Large, highly glycosylated proteins with repeat tandem domains rich in serine and threonine sites for O-glycosylation
  • Also contain glyco-conjugates (mucoproteins, glycoproteins, glycosaminoglycans, glycolipids) with high content of sialic acid (N-acyl derivative of neuraminic acid) or sulfated polysaccharide
  • Neuraminic acid is a 9 carbon amino sugar derived from mannosamine and pyruvate
  • Mucin stains highlight carbohydrate portion of glycoproteins, not the protein component
  • Best pan mucin combination may be PAS and Alcian blue
  • MUC:
    • Epithelial mucins, share a common characteristic of an elevated number of sequences repeated in tandem, that are different for each MUC
  • Two main families of MUC genes:
    • Gel forming / secreted mucins at locus 11p15 (MUC2, MUC5AC, MUC5B, MUC6)
    • Membrane bound mucins at locus 7q22, 3q and 1q21 (MUC1, MUC3A, MUC3B, MUC4, MUC12, MUC13, MUC17)
  • Mucin types include acid mucins and neutral mucins
  • Acid mucins:
    • Acid-simple non-sulfated:
      • Contain sialic acid
      • Found in epithelium (gallbladder [benign, adenocarcinoma], intestinal metaplasia in stomach)
      • Positive for PAS, Alcian blue at pH 2.5, colloidal iron, and metachromatic dyes
      • They resist hyaluronidase digestion
    • Acid-simple mesenchymal:
      • Contain hyaluronic acid and digest with hyaluronic acid
      • Found in tissue stroma and sarcomas
      • Positive for Alcian blue at pH 2.5, colloidal iron, and metachromatic dyes
      • Negative for PAS
    • Acid-complex sulfated:
      • Found in adenocarcinomas
      • Usually positive for PAS, Alcian blue at pH 1, colloidal iron, mucicarmine, and metachromatic stains
      • They resist hyaluronidase digestion
    • Acid-complex connective tissue:
      • Found in tissue stroma, cartilage, and bone
      • Includes chondroitin sulfate, keratan sulfate
      • Positive for Alcian blue at pH 0.5
      • Negative for PAS
  • Neutral mucins:
    • GI tract, prostate
    • Stain with PAS only (negative for Alcian blue, colloidal iron, mucicarmine, or metachromatic dyes)
    • Note that thyroglobulin and other neutral glycoproteins are also PAS positive
Uses by Pathologists
  • Mucin stains:
    • Alcian blue:
      • Stains acid-simple non-sulfated and acid-simple mesenchymal mucins at pH 2.5, acid-complex sulfated mucins at pH 1.0 and acid-complex connective tissue mucins at pH 0.5
      • Does NOT stain neutral mucins
    • Colloidal iron:
      • Stains acid-simple non-sulfated, acid-simple mesenchymal, acid-complex sulfated mucins
      • Does NOT stain neutral mucins or acid-complex connective tissue mucins
      • Theory: acid mucopolysaccharides attract iron particles stabilized in ammonia and glycerin
      • Requires formalin fixation
      • False positives include phospholipids and free nucleic acids
      • More specific if hyaluronidase pre-digestion
      • For chromophobe carcinomas, have diffuse strong staining with reticular pattern
    • Mucicarmine:
      • Very specific for epithelial mucins, including adenocarcinomas
      • Although insensitive
      • Atain contains carmine (red coloring material) and aluminum chloride
    • PAS (periodic acid-Schiff):
      • Stains glycogen as well as mucins, but tissue can be pre-digested with diastase to remove glycogen
      • Stains neutral and acid-simple non-sulfated and acid-complex sulfated mucins
      • Does NOT stain acid-simple mesenchymal mucins and acid-complex connective tissue mucins
Additional References