title: Screening for Lynch syndrome and referral to clinical genetics by selective mismatch repair protein immunohistochemistry testing: an audit and cost analysis.
abstract: Lynch syndrome (LS) accounts for around 3% of colorectal cancers (CRCs) and is caused by germline mutations in mismatch repair (MMR) genes. Recently, screening strategies to identify patients with LS have become popular. We audited CRCs screened with MMR immunohistochemistry (IHC) in 2013. 209 tumours had MMR IHC performed at a cost of £12 540. 47/209 (21%) cases showed IHC loss of expression in at least one MMR protein. 28/44 cases with loss of MLH1 had additional BRAF V600E testing, at a cost of £5040. MMR IHC reduced the number of potential clinical genetics referrals from 209 to 47. BRAF mutation testing, performed in a subset of cases with MLH1 loss, further reduced this to 21. At a cost of £1340 per referral, this model of LS screening for clinical genetics referral had significant potential savings (£234 340) and can be easily implemented in parallel with MMR IHC done for prognostication in CRCs.
authors.affiliation: Nuffield Division of Clinical Laboratory Sciences, University of Oxford, Oxford, UK.
authors.forename: Richard
authors.initials: R
authors.lastname: Colling
authors.affiliation: Oxford Cancer Centre, University of Oxford, Oxford, UK.
authors.forename: David N
authors.initials: DN
authors.lastname: Church
authors.affiliation: Oxford Cancer Centre, University of Oxford, Oxford, UK.
authors.forename: Juliet
authors.initials: J
authors.lastname: Carmichael
authors.affiliation: Department of Cellular Pathology, Oxford University Hospitals NHS Trust, Oxford, UK.
authors.forename: Lucinda
authors.initials: L
authors.lastname: Murphy
authors.affiliation: Department of Gastroenterology, Oxford University Hospitals NHS Trust, Oxford, UK.
authors.forename: James
authors.initials: J
authors.lastname: East
authors.affiliation: Department of Genetics, Oxford University Hospitals NHS Trust, Oxford, UK.
authors.forename: Peter
authors.initials: P
authors.lastname: Risby
authors.affiliation: Oxford Cancer Centre, University of Oxford, Oxford, UK.
authors.forename: Rachel
authors.initials: R
authors.lastname: Kerr
authors.affiliation: Department of Pathology, University Health Network, Toronto, Ontario, Canada.
authors.forename: Runjan
authors.initials: R
authors.lastname: Chetty
authors.affiliation: Department of Cellular Pathology, Oxford University Hospitals NHS Trust, Oxford, UK.
authors.forename: Lai Mun
authors.initials: LM
authors.lastname: Wang
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis / Q000235:genetics; D015179:Colorectal Neoplasms / Q000175:diagnosis / Q000235:genetics; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000175:diagnosis* / Q000235:genetics; D003365:Costs and Cost Analysis; D053843:DNA Mismatch Repair / Q000235:genetics*; D005820:Genetic Testing / Q000191:economics / Q000379:methods; D018095:Germ-Line Mutation / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry / Q000191:economics; D008403:Mass Screening / Q000191:economics / Q000379:methods; D008485:Medical Audit / Q000191:economics; D053842:Microsatellite Instability; D011379:Prognosis; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D012017:Referral and Consultation; D012189:Retrospective Studies
chemical_list: C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf
keywords: AUDIT; COLORECTAL CANCER; QUALITY ASSURANCE