title: Discordant Mismatch Repair Protein Immunoreactivity in Lynch Syndrome-Associated Neoplasms:  A Recommendation for Screening Synchronous/Metachronous Neoplasms.
abstract: OBJECTIVE
  Lynch syndrome (LS) predisposes individuals to developing synchronous and metachronous LS-associated neoplasms (LSANs). Mismatch repair protein (MMRP) immunohistochemistry (IHC) is widely used to identify LS, but its utility in patients with synchronous/metachronous lesions has not been studied. We studied MMRP IHC in patients with LS with more than one LSAN to provide screening recommendations in patients with synchronous/metachronous neoplasms.
  
  
  METHODS
  All patients with LS diagnosed at The Ohio State University Wexner Medical Center from 2009 through 2014 with more than one LSAN and available tumor tissue for immunostaining were identified. Tumors were stained for MLH1, MSH2, MSH6, and PMS-2 proteins, and immunoreactivity was scored as intact or lost.
  
  
  RESULTS
  Thirteen patients with LS with 29 synchronous and/or metachronous primary LSANs were identified. Neoplasms involved large and small intestine (n = 19), ampulla (n = 1), endometrium (n = 1), and skin (sebaceous neoplasms, n = 8). Nine (69%) of 13 patients showed concordant MMRP results in all tumors, and four (31%) showed discordant MMRP results.
  
  
  CONCLUSIONS
  LS diagnosis could have been missed in 31% of the study cases if only the LSAN exhibiting intact MMRP expression was screened. Accordingly, our findings support the recommendation to perform LS screening in all primary, synchronous, and metachronous intestinal and endometrial cancers if a previous tumor screened intact.
authors.affiliation: From the Department of Pathology.
authors.forename: Rachel M
authors.initials: RM
authors.lastname: Roth
authors.affiliation: Division of Medical Oncology, Department of Internal Medicine, Stanford University, Stanford, CA.
authors.forename: Sigurdis
authors.initials: S
authors.lastname: Haraldsdottir
authors.affiliation: Division of Human Genetics, Department of Internal Medicine, The Ohio State University Medical Center, Columbus.
authors.forename: Heather
authors.initials: H
authors.lastname: Hampel
authors.affiliation: From the Department of Pathology.
authors.forename: Christina A
authors.initials: CA
authors.lastname: Arnold
authors.affiliation: From the Department of Pathology wendy.frankel@osumc.edu.
authors.forename: Wendy L
authors.initials: WL
authors.lastname: Frankel
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000175:diagnosis* / Q000235:genetics; D053843:DNA Mismatch Repair / Q000235:genetics; D045643:DNA Repair Enzymes / Q000032:analysis*; D055088:Early Detection of Cancer / Q000379:methods*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D045643:DNA Repair Enzymes
keywords: Cancer screening; Lynch syndrome; Metachronous cancer; Mismatch repair proteins; Synchronous cancer