title: Pathology features in Bethesda guidelines predict colorectal cancer microsatellite instability: a population-based study.
abstract: OBJECTIVE
  The revised Bethesda guidelines for Lynch syndrome recommend microsatellite instability (MSI) testing all colorectal cancers in patients diagnosed before age 50 years and colorectal cancers diagnosed in patients between ages 50 and 59 years with particular pathology features. Our aim was to identify pathology and other features that independently predict high MSI (MSI-H).
  
  
  METHODS
  Archival tissue from 1098 population-based colorectal cancers diagnosed before age 60 years was tested for MSI. Pathology features, site, and age at diagnosis were obtained. Multiple logistic regression was performed to determine the predictive value of each feature, as measured by an odds ratio (OR), from which a scoring system (MsPath) was developed to estimate the probability a colorectal cancer is MSI-H.
  
  
  RESULTS
  Fifteen percent of tumors (162) were MSI-H. Independent predictors were tumor-infiltrating lymphocytes (OR, 9.1; 95% confidence interval [CI], 5.9-14.1), proximal subsite (OR, 4.7; 95% CI, 3.1-7.3), mucinous histology (OR, 2.8; 95% CI, 1.7-4.8), poor differentiation (OR, 1.9; 95% CI, 1.2-3.1), Crohn's-like reaction (OR, 1.9; 95% CI, 1.2-2.9), and diagnosis before age 50 years (OR, 1.9; 95% CI, 1.3-2.9). MsPath score >or=1.0 had a sensitivity of 93% and a specificity of 55% for MSI-H.
  
  
  CONCLUSIONS
  The probability an individual colorectal cancer is MSI-H is predicted well by the MsPath score. There is little value in testing for DNA mismatch repair loss in tumors, or for germline mismatch repair mutations, for colorectal cancers diagnosed in patients before age 60 years with an MSPath score <1 (approximately 50%). Pathology can identify almost all MSI-H colorectal cancers diagnosed before age 60 years.
authors.affiliation: Centre for Molecular, Environmental, Genetic and Analytic Epidemiology, University of Melbourne, Parkville, Victoria, Australia. m.jenkins@unimelb.edu.au <m.jenkins@unimelb.edu.au>
authors.forename: Mark A
authors.initials: MA
authors.lastname: Jenkins
authors.forename: Shinichi
authors.initials: S
authors.lastname: Hayashi
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: O'Shea
authors.forename: Lawrence J
authors.initials: LJ
authors.lastname: Burgart
authors.forename: Tom C
authors.initials: TC
authors.lastname: Smyrk
authors.forename: David
authors.initials: D
authors.lastname: Shimizu
authors.forename: Paul M
authors.initials: PM
authors.lastname: Waring
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Ruszkiewicz
authors.forename: Aaron F
authors.initials: AF
authors.lastname: Pollett
authors.forename: Mark
authors.initials: M
authors.lastname: Redston
authors.forename: Melissa A
authors.initials: MA
authors.lastname: Barker
authors.forename: John A
authors.initials: JA
authors.lastname: Baron
authors.forename: Graham R
authors.initials: GR
authors.lastname: Casey
authors.forename: James G
authors.initials: JG
authors.lastname: Dowty
authors.forename: Graham G
authors.initials: GG
authors.lastname: Giles
authors.forename: Paul
authors.initials: P
authors.lastname: Limburg
authors.forename: Polly
authors.initials: P
authors.lastname: Newcomb
authors.forename: Joanne P
authors.initials: JP
authors.lastname: Young
authors.forename: Michael D
authors.initials: MD
authors.lastname: Walsh
authors.forename: Stephen N
authors.initials: SN
authors.lastname: Thibodeau
authors.forename: Noralane M
authors.initials: NM
authors.lastname: Lindor
authors.forename: Loïc
authors.initials: L
authors.lastname: Lemarchand
authors.forename: Steven
authors.initials: S
authors.lastname: Gallinger
authors.forename: Robert W
authors.initials: RW
authors.lastname: Haile
authors.forename: John D
authors.initials: JD
authors.lastname: Potter
authors.forename: John L
authors.initials: JL
authors.lastname: Hopper
authors.forename: Jeremy R
authors.initials: JR
authors.lastname: Jass
mesh_terms: D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000235:genetics* / Q000473:pathology*; D004273:DNA, Neoplasm / Q000032:analysis / Q000235:genetics; D005260:Female; D005762:Gastroenterology / Q000592:standards*; D006801:Humans; D008297:Male; D008495:Medical Oncology / Q000592:standards; D053842:Microsatellite Instability; D008875:Middle Aged; D008957:Models, Genetic; D017410:Practice Guidelines as Topic / Q000592:standards*; D011237:Predictive Value of Tests; D011336:Probability; D015203:Reproducibility of Results
chemical_list: D004273:DNA, Neoplasm