title: Value of microsatellite instability typing in detecting hereditary non-polyposis colorectal cancer. A prospective multicentric study by the Association Aquitaine Gastro.
abstract: OBJECTIVE
  To detect hereditary non-polyposis colorectal cancer (HNPCC) patients with a strategy combining clinical selection (patient age at onset of cancer less than 50 years or family history of HNPCC tumors) and microsatellite instability typing plus immunohistochemistry, leading to mismatch repair (MMR) germline mutation analysis.
  
  
  METHODS
  Tumors were screened for microsatellite instability (MSI) and for hmlh1 and hmsh2 immunohistochemical expression. Germline mutation analysis was performed to search for MLH1 and MSH2 mutations in patients with MSI-High and MSI-Low tumors.
  
  
  RESULTS
  197 adenocarcinomas were studied: 164 patients were< or =50 years old, 33 were older than 50 years but had a family history of HNPCC tumors. Fifty tumors (25.4%) were MSI-High, 10 were MSI-Low (5.1%), and 130 were MS-Stable (66%). MSI typing was inconclusive in 7 (3.5%). Immunohistochemistry screening was performed on 165 tumors: sensitivity was 63.6%, specificity was 99%. Germline mutation analysis was performed in 33/60 MSI-High or Low tumors: 23 mutations were noted (70% of the tested patients).
  
  
  CONCLUSIONS
  This proposed strategy of determining microsatellite instability in young colorectal cancer patients or in patients with a family history of HNPCC tumors led to an increased frequency in the detection of MMR germline mutations.
authors.affiliation: Département d'Oncologie Digestive, Institut Bergonié, Bordeaux, France. becouarn@bergonie.org
authors.forename: Yves
authors.initials: Y
authors.lastname: Bécouarn
authors.forename: Anne
authors.initials: A
authors.lastname: Rullier
authors.forename: Philippe
authors.initials: P
authors.lastname: Gorry
authors.forename: Denis
authors.initials: D
authors.lastname: Smith
authors.forename: Bruno
authors.initials: B
authors.lastname: Richard-Molard
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Echinard
authors.forename: Patrick
authors.initials: P
authors.lastname: Texereau
authors.forename: Richard
authors.initials: R
authors.lastname: Beyssac
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Legoux
authors.forename: Hervé
authors.initials: H
authors.lastname: Lamouliatte
authors.forename: Thierry
authors.initials: T
authors.lastname: Frebourg
authors.forename: Sylviane
authors.initials: S
authors.lastname: Olschwang
authors.forename: Brigitte
authors.initials: B
authors.lastname: Gilbert
authors.forename: Laurence
authors.initials: L
authors.lastname: Venat
authors.forename: Véronique
authors.initials: V
authors.lastname: Picot
authors.forename: François
authors.initials: F
authors.lastname: Paraf
authors.forename: Michel
authors.initials: M
authors.lastname: Longy
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis* / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D020137:Base Pair Mismatch / Q000235:genetics; D043171:Chromosomal Instability; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000175:diagnosis* / Q000235:genetics*; D004260:DNA Repair; D005260:Female; D018095:Germ-Line Mutation; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics*; D008875:Middle Aged; D010375:Pedigree; D011446:Prospective Studies