title: Simplified identification of Lynch syndrome: a prospective, multicenter study.
abstract: BACKGROUND
  Recommended strategies to screen for Lynch syndrome in colorectal cancer are not applied in daily practice and most of Lynch cases remain undiagnosed.
  
  
  OBJECTIVE
  We investigated in routine conditions a strategy that uses simplified clinical criteria plus detection of MisMatch Repair deficiency in tumours to identify Lynch carriers.
  
  
  METHODS
  Colorectal cancer patients that met at least one of three clinical criteria were included: (1) colorectal cancer before 50 years, (2) personal history of colorectal or endometrial cancer, (3) first-degree relative history of colorectal or endometrial cancer. All tumours underwent an MisMatch Repair test combining microsatellite instability analysis and MisMatch Repair immunohistochemistry. Patients with an MisMatch Repair-deficient tumour were offered germline testing.
  
  
  RESULTS
  Of the 307 patients fulfilling the clinical criteria, 46 (15%) had a MisMatch Repair-deficient tumour. Amongst them 27 were identified as Lynch carriers (20 with germline mutation: 12 MLH1, 7 MSH2, 1 MSH6; 7 highly suspected cases despite failure of genetic testing). The simplified clinical criteria selected a population whose MisMatch Repair-deficient status was highly predictive (59%) of Lynch syndrome.
  
  
  CONCLUSIONS
  This bio-clinical strategy based on simplified clinical criteria combined with an MisMatch Repair test efficiently detected LS cases and is easy to use in clinical practice, outside expert centres.
authors.affiliation: Purpan Hospital, Medical Oncology, Institut Claudius Regaud, Medical Genetics, Cancer Research Centre of Toulouse, INSERM UMR 1037/CNRS-ERL 5294/Toulouse 3 University, Markers & Targets for Digestive Cancer Biotherapy, Toulouse, France.
authors.forename: Delphine
authors.initials: D
authors.lastname: Bonnet
authors.forename: Janick
authors.initials: J
authors.lastname: Selves
authors.forename: Christine
authors.initials: C
authors.lastname: Toulas
authors.forename: Marie
authors.initials: M
authors.lastname: Danjoux
authors.forename: Jean Pierre
authors.initials: JP
authors.lastname: Duffas
authors.forename: Guillaume
authors.initials: G
authors.lastname: Portier
authors.forename: Sylvain
authors.initials: S
authors.lastname: Kirzin
authors.forename: Laurent
authors.initials: L
authors.lastname: Ghouti
authors.forename: Nicolas
authors.initials: N
authors.lastname: Carrère
authors.forename: Bertrand
authors.initials: B
authors.lastname: Suc
authors.forename: Laurent
authors.initials: L
authors.lastname: Alric
authors.forename: Karl
authors.initials: K
authors.lastname: Barange
authors.forename: Louis
authors.initials: L
authors.lastname: Buscail
authors.forename: Thierry
authors.initials: T
authors.lastname: Chaubard
authors.forename: Kamran
authors.initials: K
authors.lastname: Imani
authors.forename: Rosine
authors.initials: R
authors.lastname: Guimbaud
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D000230:Adenocarcinoma / Q000175:diagnosis* / Q000235:genetics*; D000328:Adult; D000367:Age Factors; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000175:diagnosis* / Q000235:genetics*; D053843:DNA Mismatch Repair; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000235:genetics; D016889:Endometrial Neoplasms / Q000235:genetics*; D005260:Female; D005820:Genetic Testing; D018095:Germ-Line Mutation; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D053842:Microsatellite Instability; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics; D018579:Patient Selection; D011237:Predictive Value of Tests; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D004268:DNA-Binding Proteins; C094443:G-T mismatch-binding protein; C501486:MLH1 protein, human; D009687:Nuclear Proteins; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; C497172:MSH2 protein, human; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein