title: Efficiency of the revised Bethesda guidelines (2003) for the detection of mutations in mismatch repair genes in Austrian HNPCC patients.
abstract: The clinical diagnosis of hereditary nonpolyposis colorectal cancer (HNPCC) is based on the Amsterdam II criteria (ACII). The purpose of using the Bethesda guidelines (BG) is to select tumours for microsatellite analysis. Recently, the modified Amsterdam criteria (ACmod) and Bethesda guidelines (BGmod) were proposed to simplify definitions. We evaluated the efficiency of the ACmod and BGmod to identify patients with germ-line mutations in MLH1 and MSH2 in 81 unrelated Austrian HNPCC families. Microsatellite (MS) analysis was performed in 55 tumours. The new criteria included more families than the old ones: BGmod, n = 81; BG, n = 72; ACmod, n = 52 and ACII, n = 35. The more stringent old criteria tended to show greater positive predictive value for association with a germ-line mutation than the corresponding new criteria: BGmod, 23%; BG, 26%; ACmod, 31% and ACII, 37%. The larger number of patients analysed in the ACmod group resulted in greater sensitivity compared to the ACII. The increased workload for BGmod was not associated with greater sensitivity. Microsatellite instability (MSI) significantly enhanced specificity in all subgroups. We recommend the use of the ACmod criteria to select patients for primary sequence analysis, when microsatellite analysis is not possible. If the BG are used, we suggest that BG be given preference over BGmod, as the former signify a lesser workload.
authors.affiliation: Medical University of Vienna, Department of Surgery, Research Laboratories, Austria.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Wolf
authors.forename: Silke
authors.initials: S
authors.lastname: Gruber
authors.forename: Silvia
authors.initials: S
authors.lastname: Henglmueller
authors.forename: Sonja
authors.initials: S
authors.lastname: Kappel
authors.forename: Michael
authors.initials: M
authors.lastname: Bergmann
authors.forename: Friedrich
authors.initials: F
authors.lastname: Wrba
authors.forename: Judith
authors.initials: J
authors.lastname: Karner-Hanusch
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D001317:Austria; D002352:Carrier Proteins / Q000235:genetics*; D015331:Cohort Studies; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000235:genetics* / Q000473:pathology; D053843:DNA Mismatch Repair; D004252:DNA Mutational Analysis / Q000379:methods*; D005260:Female; D005787:Gene Frequency; D018095:Germ-Line Mutation; D017408:Guidelines as Topic / Q000592:standards*; D006801:Humans; D008297:Male; D053842:Microsatellite Instability; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D015203:Reproducibility of Results
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; C501486:MLH1 protein, human; D009687:Nuclear Proteins; C497172:MSH2 protein, human; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein