title: Heterogenous mismatch-repair status in colorectal cancer.
abstract: BACKGROUND
  Immunohistochemical staining for mismatch repair proteins is efficient and widely used to identify mismatch repair defective tumors. The tumors typically show uniform and widespread loss of MMR protein staining. We identified and characterized colorectal cancers with alternative, heterogenous mismatch repair protein staining in order to delineate expression patterns and underlying mechanisms.
  
  
  METHODS
  Heterogenous staining patterns that affected at least one of the mismatch repair proteins MLH1, PMS2, MSH2 and MSH6 were identified in 14 colorectal cancers. Based on alternative expression patterns macro-dissected and micro-dissected tumor areas were separately analyzed for microsatellite instability and MLH1 promoter methylation.
  
  
  RESULTS
  Heterogenous retained/lost mismatch repair protein expression could be classified as intraglandular (within or in-between glandular formations), clonal (in whole glands or groups of glands) and compartmental (in larger tumor areas/compartments or in between different tumor blocks). These patterns coexisted in 9/14 tumors and in the majority of the tumors correlated with differences in microsatellite instability/MLH1 methylation status.
  
  
  CONCLUSIONS
  Heterogenous mismatch repair status can be demonstrated in colorectal cancer. Though rare, attention to this phenomenon is recommended since it corresponds to differences in mismatch repair status that are relevant for correct classification.
  The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1771940323126788.
authors: Department of Oncology and Pathology, Institute of Clinical Sciences, Lund University, SE-22381, Lund, Sweden. patrick.joost@med.lu.se.
authors: Patrick
authors: P
authors: Joost
authors: Nynke
authors: N
authors: Veurink
authors: Susanne
authors: S
authors: Holck
authors: Louise
authors: L
authors: Klarskov
authors: Anders
authors: A
authors: Bojesen
authors: Maria
authors: M
authors: Harbo
authors: Bo
authors: B
authors: Baldetorp
authors: Eva
authors: E
authors: Rambech
authors: Mef
authors: M
authors: Nilbert
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000032:analysis / Q000235:genetics; D000251:Adenosine Triphosphatases / Q000032:analysis; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D020137:Base Pair Mismatch; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics; D015179:Colorectal Neoplasms / Q000737:chemistry* / Q000235:genetics / Q000473:pathology; D019175:DNA Methylation; D045643:DNA Repair Enzymes / Q000032:analysis; D004268:DNA-Binding Proteins / Q000032:analysis; D003718:Denmark; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D053842:Microsatellite Instability; D008875:Middle Aged; D000070976:Mismatch Repair Endonuclease PMS2; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein / Q000032:analysis; D009687:Nuclear Proteins / Q000032:analysis / Q000235:genetics; D011401:Promoter Regions, Genetic; D013548:Sweden
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; C094443:G-T mismatch-binding protein; C501486:MLH1 protein, human; D009687:Nuclear Proteins; D000251:Adenosine Triphosphatases; C094934:PMS2 protein, human; C497172:MSH2 protein, human; D000070976:Mismatch Repair Endonuclease PMS2; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein; D045643:DNA Repair Enzymes