title: Morphology of sporadic colorectal cancer with DNA replication errors.
abstract: BACKGROUND
  Up to 15% of colorectal cancers are characterised by DNA microsatellite instability (MIN), shown by the presence of DNA replication errors (RERs).
  
  
  OBJECTIVE
  To identify pathological features that are discriminating for colorectal cancer (CRC) showing extensive MIN.
  
  
  METHODS
  A prospective series of 303 patients with CRC and no family history of either familial adenomatous polyposis or hereditary non-polyposis colorectal cancer.
  
  
  METHODS
  DNA was extracted from fresh tissue samples and the presence of MIN was studied at nine loci that included TGF beta RII, IGFIIR, and BAX. The 61 cases showing RERs were compared with 63 RER negative cases with respect to a comprehensive set of clinical and pathological variables. Predictive utility of the variables was tested by decision tree analysis.
  
  
  RESULTS
  Twenty seven patients with CRC showed extensive RERs (three loci or more) (RER+) and 34 had limited RERs only (28 = one locus; 6 = two loci) (RER+/-), yielding a bimodal distribution. RER+ cancers differed from RER- and RER+/-) cases. Tumour type (adenocarcinoma, mucinous carcinoma, and undifferentiated carcinoma) (p = 0.001), tumour infiltrating lymphocytes (p = 0.001), and anatomical site (p = 0.001) were the most significant of the discriminating variables. Algorithms developed by decision tree analysis allowed cases to be assigned to RER+ versus RER- and +/- status with a global sensitivity of 81.5%, specificity of 96%, and overall accuracy of 93%.
  
  
  CONCLUSIONS
  Pathological examination of CRC allows assignment of RER+ status; assignment is specific and relatively sensitive. Conversely RER- and RER+/- CRC are indistinguishable.
authors.affiliation: Department of Pathology, University of Queensland, Australia.
authors.forename: J R
authors.initials: JR
authors.lastname: Jass
authors.forename: K A
authors.initials: KA
authors.lastname: Do
authors.forename: L A
authors.initials: LA
authors.lastname: Simms
authors.forename: H
authors.initials: H
authors.lastname: Iino
authors.forename: C
authors.initials: C
authors.lastname: Wynter
authors.forename: S P
authors.initials: SP
authors.lastname: Pillay
authors.forename: J
authors.initials: J
authors.lastname: Searle
authors.forename: G
authors.initials: G
authors.lastname: Radford-Smith
authors.forename: J
authors.initials: J
authors.lastname: Young
authors.forename: B
authors.initials: B
authors.lastname: Leggett
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000473:pathology; D002288:Adenocarcinoma, Mucinous / Q000235:genetics / Q000473:pathology; D002277:Carcinoma / Q000235:genetics / Q000473:pathology; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology*; D004261:DNA Replication; D003661:Decision Support Techniques; D006801:Humans; D018895:Microsatellite Repeats; D016133:Polymerase Chain Reaction; D011446:Prospective Studies