title: Systematic immunohistochemical screening for Lynch syndrome in colorectal cancer: a single centre experience of 486 patients.
abstract: BACKGROUND
  Germline mutations in DNA mismatch repair (MMR) genes MLH1, MSH2, MSH6 and PMS2 cause autosomal dominantly inherited Lynch syndrome. Lynch syndrome patients and their families benefit from life-saving intensive cancer surveillance. Approximately one in 30 colorectal cancers arises in the setting of Lynch syndrome.
  
  
  OBJECTIVE
  The aim of this study was to assess the detection rate of Lynch syndrome at our institution after introduction of systematic immunohistochemical screening for MMR deficiency in colorectal cancers from 2011 to 2015.
  
  
  METHODS
  Following the recommendations by the Evaluation of Genomic Applications in Practice and Prevention working group all colorectal cancers were immunohistochemically stained for the presence of MMR proteins MLH1, PMS2, MSH2 and MSH6, independent of clinical criteria. In the case of loss of MLH1, the somatic BRAF mutation V600E was assessed with molecular testing and/or immunohistochemistry. Clinical follow-up of potential Lynch syndrome carriers (patients with tumours showing loss of MLH1 expression with absence of BRAFV600E, loss of PMS2, MSH2 or MSH6) was evaluated.
  
  
  RESULTS
  Of all patients (n = 486), loss of MMR protein expression was found in 73 (15.0%) tumours. Twenty-eight (6.0%) were classified as potential Lynch syndrome carriers. Of the genetically tested potential Lynch syndrome carriers (10 out of 28 patients), 40% were first diagnosed with Lynch syndrome.
  
  
  CONCLUSIONS
  Implementation of systematic immunohistochemistry screening for Lynch syndrome showed that 6% of colorectal cancers were potentially Lynch-syndrome related. Tumour board protocols should systematically contain information on MMR status of all colorectal cancers and, in MMR deficient cases, include clear recommendations for genetic counselling for all potential Lynch syndrome patients.
authors.affiliation: Department of Surgery, St. Claraspital, Basel, Switzerland.
authors.forename: Valentin
authors.initials: V
authors.lastname: Zumstein
authors.affiliation: Department of Surgery, St. Claraspital, Basel, Switzerland.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Vinzens
authors.affiliation: Department of Pathology, Viollier AG, Allschwil, Switzerland.
authors.forename: Andreas
authors.initials: A
authors.lastname: Zettl
authors.affiliation: Department of Medical Genetics, University Hospital Basel, Switzerland.
authors.forename: Karl
authors.initials: K
authors.lastname: Heinimann
authors.affiliation: Departments of Internal Medicine and Oncology, St. Claraspital, Basel, Switzerland.
authors.forename: Dieter
authors.initials: D
authors.lastname: Koeberle
authors.affiliation: Department of Surgery, St. Claraspital, Basel, Switzerland.
authors.forename: Markus
authors.initials: M
authors.lastname: von Flüe
authors.affiliation: Department of Surgery, St. Claraspital, Basel, Switzerland.
authors.forename: Martin
authors.initials: M
authors.lastname: Bolli
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics; D053843:DNA Mismatch Repair / Q000235:genetics; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing / Q000379:methods*; D018095:Germ-Line Mutation / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods*
chemical_list: D048868:Adaptor Proteins, Signal Transducing