title: Prevalence and clinicopathologic/molecular characteristics of mismatch repair-deficient colorectal cancer in the under-50-year-old Japanese population.
abstract: OBJECTIVE
  To clarify the prevalence and clinicopathologic/molecular characteristics of mismatch repair (MMR)-deficient colorectal cancer in the young Japanese population.
  
  
  METHODS
  Immunohistochemical analyses for MMR proteins (MLH1, MSH2, MSH6, and PMS2) were performed in formalin-fixed paraffin-embedded sections prepared from the resected CRC specimens of 119 consecutive patients aged <50 years old, who underwent resection of the primary tumor at our institution between 1996 and 2015. Analyses for somatic BRAF V600E mutation, somatic hypermethylation of the MLH1 promoter, and germline MMR gene mutations were undertaken where indicated.
  
  
  RESULTS
  MMR protein loss was found in 10 patients (8.4%), 7 (5.9%) of whom were subsequently identified to have Lynch syndrome (LS). The remaining 3 patients were categorized as having sporadic MMR-deficient CRC (n = 2) or "possible LS (n = 1)". In multivariate logistic regression analysis, the presence of tumor-infiltrating lymphocytes (P < 0.01), right-sided location of the tumor (P = 0.01), and a history of LS-associated tumors in the first-degree relatives (P < 0.01) were identified as independent factors predictive of MMR-deficient CRC.
  
  
  CONCLUSIONS
  These results are of value in the clinical management of patients with the early onset CRC under circumstances where universal tumor screening approaches for LS are still not available, like in Japan.
authors.affiliation: Department of Digestive Tract and General Surgery, Saitama Medical Center, Saitama Medical University, 1981 Kamoda, Kawagoe, Saitama, 350-8550, Japan.
authors.forename: Okihide
authors.initials: O
authors.lastname: Suzuki
authors.affiliation: Genomic Research Center, Saitama Medical University, 1397-1 Yamane, Hidaka, Saitama, 350-1241, Japan.
authors.forename: Hidetaka
authors.initials: H
authors.lastname: Eguchi
authors.affiliation: Department of Digestive Tract and General Surgery, Saitama Medical Center, Saitama Medical University, 1981 Kamoda, Kawagoe, Saitama, 350-8550, Japan.
authors.forename: Noriyasu
authors.initials: N
authors.lastname: Chika
authors.affiliation: Department of Digestive Tract and General Surgery, Saitama Medical Center, Saitama Medical University, 1981 Kamoda, Kawagoe, Saitama, 350-8550, Japan.
authors.forename: Takehiko
authors.initials: T
authors.lastname: Sakimoto
authors.affiliation: Department of Digestive Tract and General Surgery, Saitama Medical Center, Saitama Medical University, 1981 Kamoda, Kawagoe, Saitama, 350-8550, Japan.
authors.forename: Keiichiro
authors.initials: K
authors.lastname: Ishibashi
authors.affiliation: Department of Digestive Tract and General Surgery, Saitama Medical Center, Saitama Medical University, 1981 Kamoda, Kawagoe, Saitama, 350-8550, Japan.
authors.forename: Kensuke
authors.initials: K
authors.lastname: Kumamoto
authors.affiliation: Department of Pathology, Saitama Medical Center, Saitama Medical University, Saitama, Japan.
authors.forename: Jun-Ichi
authors.initials: JI
authors.lastname: Tamaru
authors.affiliation: Department of Cancer Prevention and Molecular Genetics, Saitama Prefectural Cancer Center, Saitama, Japan.
authors.forename: Tetsuhiko
authors.initials: T
authors.lastname: Tachikawa
authors.affiliation: Department of Cancer Prevention and Molecular Genetics, Saitama Prefectural Cancer Center, Saitama, Japan.
authors.forename: Kiwamu
authors.initials: K
authors.lastname: Akagi
authors.affiliation: Department of Pathology, Tokyo Metropolitan Geriatric Hospital, Tokyo, Japan.
authors.forename: Tomio
authors.initials: T
authors.lastname: Arai
authors.affiliation: Genomic Research Center, Saitama Medical University, 1397-1 Yamane, Hidaka, Saitama, 350-1241, Japan. okazaki@saitama-med.ac.jp.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Okazaki
authors.affiliation: Department of Digestive Tract and General Surgery, Saitama Medical Center, Saitama Medical University, 1981 Kamoda, Kawagoe, Saitama, 350-8550, Japan. 05hishi@saitama-med.ac.jp.
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Ishida
mesh_terms: D000328:Adult; D000367:Age Factors; D001932:Brain Neoplasms / Q000453:epidemiology* / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000453:epidemiology* / Q000235:genetics* / Q000473:pathology; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000235:genetics / Q000473:pathology; D053843:DNA Mismatch Repair / Q000235:genetics; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007564:Japan / Q000453:epidemiology; D016015:Logistic Models; D016246:Lymphocytes, Tumor-Infiltrating / Q000473:pathology; D008297:Male; D008875:Middle Aged; D000070957:MutL Protein Homolog 1 / Q000235:genetics; D009154:Mutation; D009386:Neoplastic Syndromes, Hereditary / Q000453:epidemiology* / Q000235:genetics*; D015995:Prevalence; D011401:Promoter Regions, Genetic; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics
chemical_list: C501486:MLH1 protein, human; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D000070957:MutL Protein Homolog 1
keywords: Colorectal cancer; Immunohistochemistry; Lynch syndrome; Mismatch repair deficiency; Young population