title: Quality assessment and correlation of microsatellite instability and immunohistochemical markers among population- and clinic-based colorectal tumors results from the Colon Cancer Family Registry.
abstract: The detection of defective mismatch repair (MMR), as assessed by the presence of tumor microsatellite instability (MSI) and/or loss of MMR protein expression by IHC, has been useful for risk assessment, prognosis, and prediction of treatment in patients with colorectal cancer. We analyzed tumors for the presence of defective MMR from 5927 Colorectal Cancer Family Registry patients recruited at six international consortium sites. We evaluated the appropriate percentage instability cutoff used to distinguish the three MSI phenotypes [ie, stable (MSS), low instability (MSI-L), and high instability (MSI-H)]; the sensitivity, specificity, and performance characteristics of individual markers; and the concordance between MSI and IHC phenotypes. Guided by the results of the IHC testing, our findings indicate that the distinction between an MSI-H phenotype from a low-instability or MSS phenotype can best be accomplished by using a cutoff of 30% or greater of the markers showing instability. The sensitivity and specificity of the mononucleotide markers were higher than those of the dinucleotide markers. Specifically, BAT26 and BAT25 had the highest sensitivity (94%) and specificity (98%), and the use of mononucleotide markers alone identified 97% of the MSI-H cases correctly. As expected, the presence of MSI-H correlated with an older age of diagnosis, the presence of tumor in the proximal colon, and female sex.
authors.affiliation: Division of Experimental Pathology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA.
authors.forename: Mine S
authors.initials: MS
authors.lastname: Cicek
authors.forename: Noralane M
authors.initials: NM
authors.lastname: Lindor
authors.forename: Steven
authors.initials: S
authors.lastname: Gallinger
authors.forename: Bharati
authors.initials: B
authors.lastname: Bapat
authors.forename: John L
authors.initials: JL
authors.lastname: Hopper
authors.forename: Mark A
authors.initials: MA
authors.lastname: Jenkins
authors.forename: Joanne
authors.initials: J
authors.lastname: Young
authors.forename: Daniel
authors.initials: D
authors.lastname: Buchanan
authors.forename: Michael D
authors.initials: MD
authors.lastname: Walsh
authors.forename: Loic
authors.initials: L
authors.lastname: Le Marchand
authors.forename: Terrilea
authors.initials: T
authors.lastname: Burnett
authors.forename: Polly A
authors.initials: PA
authors.lastname: Newcomb
authors.forename: William M
authors.initials: WM
authors.lastname: Grady
authors.forename: Robert W
authors.initials: RW
authors.lastname: Haile
authors.forename: Graham
authors.initials: G
authors.lastname: Casey
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Plummer
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Krumroy
authors.forename: John A
authors.initials: JA
authors.lastname: Baron
authors.forename: Stephen N
authors.initials: SN
authors.lastname: Thibodeau
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism*; D015179:Colorectal Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D008297:Male; D053842:Microsatellite Instability; D018895:Microsatellite Repeats / Q000235:genetics; D008875:Middle Aged; D010641:Phenotype; D011785:Quality Assurance, Health Care; D012016:Reference Values; D012042:Registries; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D012737:Sex Factors; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor