title: Mismatch repair deficiency in Lynch syndrome-associated colorectal adenomas is more prevalent in older patients.
abstract: OBJECTIVE
  The aim of this study was to examine the expression of mismatch repair (MMR) proteins in Lynch syndrome (LS)-associated colorectal adenomas and to evaluate their relationship with clinicopathological variables and potential utility in LS screening.
  
  
  RESULTS
  We performed immunohistochemistry for MLH1, PMS2, MSH2 and MSH6 in 134 adenomas obtained from 26 genetically confirmed LS patients. MMR deficiency, as determined by loss of any MMR protein, was observed in 113 adenomas (84%). All the MMR-deficient adenomas exhibited homogeneous loss of MMR proteins, which reflected underlying germline mutations. MMR deficiency was more frequent in adenomas obtained from older patients (aged ≥60 years; 81 of 86, 94%), with larger tumour size (>5 mm; 71 of 73, 97%) and with high-grade dysplasia (50 of 51, 98%). Multivariate analyses indicated that increased age and larger tumour size were associated independently with MMR deficiency.
  
  
  CONCLUSIONS
  This study shows that MMR deficiency is associated significantly with increased age, in addition to two previously reported factors-larger size and high-grade dysplasia. When adenomas are analysed during LS screening, high sensitivity is expected if the adenomas are associated with any of these three factors.
authors.affiliation: Division of Pathology and Clinical Laboratories, National Cancer Center Hospital, Tokyo, Japan.|Division of Colorectal Surgery, National Cancer Center Hospital, Tokyo, Japan.|Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Tanaka
authors.affiliation: Division of Endoscopy, National Cancer Center Hospital, Tokyo, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Nakajima
authors.affiliation: Oncogene Research Unit/Cancer Prevention Unit, Tochigi Cancer Center Research Institute, Tochigi, Japan.
authors.forename: Kokichi
authors.initials: K
authors.lastname: Sugano
authors.affiliation: Division of Genetics, National Cancer Center Research Institute, Tokyo, Japan.
authors.forename: Teruhiko
authors.initials: T
authors.lastname: Yoshida
authors.affiliation: Division of Pathology and Clinical Laboratories, National Cancer Center Hospital, Tokyo, Japan.
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Taniguchi
authors.affiliation: Division of Colorectal Surgery, National Cancer Center Hospital, Tokyo, Japan.
authors.forename: Yukihide
authors.initials: Y
authors.lastname: Kanemitsu
authors.affiliation: Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Nagino
authors.affiliation: Division of Pathology and Clinical Laboratories, National Cancer Center Hospital, Tokyo, Japan.|Division of Molecular Pathology, National Cancer Center Research Institute, Tokyo, Japan.
authors.forename: Shigeki
authors.initials: S
authors.lastname: Sekine
mesh_terms: D000236:Adenoma / Q000175:diagnosis / Q000235:genetics*; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D001932:Brain Neoplasms / Q000175:diagnosis / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000175:diagnosis / Q000235:genetics*; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000175:diagnosis* / Q000378:metabolism; D053843:DNA Mismatch Repair; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D018095:Germ-Line Mutation; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D000070976:Mismatch Repair Endonuclease PMS2 / Q000235:genetics / Q000378:metabolism; D000070957:MutL Protein Homolog 1 / Q000235:genetics / Q000378:metabolism; D051718:MutS Homolog 2 Protein / Q000235:genetics / Q000378:metabolism; D009386:Neoplastic Syndromes, Hereditary / Q000175:diagnosis / Q000235:genetics*; D015995:Prevalence
chemical_list: D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; C094443:G-T mismatch-binding protein; C501486:MLH1 protein, human; C094934:PMS2 protein, human; C497172:MSH2 protein, human; D000070976:Mismatch Repair Endonuclease PMS2; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein
keywords: Lynch syndrome; adenoma; colorectum; immunohistochemistry; mismatch repair