title: Lynch syndrome-related small intestinal adenocarcinomas.
abstract: Lynch syndrome is an autosomal-dominant disorder caused by defective DNA mismatch repair (MMR) genes and is associated with increased risk of malignancies in multiple organs. Small-intestinal adenocarcinomas are common initial manifestations of Lynch syndrome. To define the incidence and characteristics of Lynch syndrome-related small-intestinal adenocarcinomas, meticulous familial and clinical histories were obtained from 195 patients with small-intestinal adenocarcinoma, and MMR protein immunohistochemistry, microsatellite instability, MLH1 methylation, and germline mutational analyses were performed. Lynch syndrome was confirmed in eight patients (4%), all of whom had synchronous/metachronous malignancies without noticeable familial histories. Small-intestinal adenocarcinomas were the first clinical manifestation in 37% (3/8) of Lynch syndrome patients, and second malignancies developed within 5 years in 63% (5/8). The patients with accompanying Lynch syndrome were younger (≤50 years; P=0.04) and more likely to have mucinous adenocarcinomas (P=0.003), and tended to survive longer (P=0.11) than those with sporadic cases. A meticulous patient history taking, MMR protein immunolabeling, and germline MMR gene mutational analysis are important for the diagnosis of Lynch syndrome-related small-intestinal adenocarcinomas. Identifying Lynch syndrome in patients with small-intestinal adenocarcinoma can be beneficial for the early detection and treatment of additional Lynch syndrome-related cancers, especially in patients who are young or have mucinous adenocarcinomas.
authors.affiliation: Department of Pathology, Incheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Incheon, Korea.
authors.forename: Sun-Young
authors.initials: SY
authors.lastname: Jun
authors.affiliation: Institute of Catholic Integrative Medicine, Incheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Incheon, Korea.
authors.forename: Eui-Jin
authors.initials: EJ
authors.lastname: Lee
authors.affiliation: Asan Institute for Life Science, Asan Medical Center, Seoul, Korea.
authors.forename: Mi-Ju
authors.initials: MJ
authors.lastname: Kim
authors.affiliation: Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Sung Min
authors.initials: SM
authors.lastname: Chun
authors.affiliation: Department of Pathology, Yeungnam University College of Medicine, Daegu, Korea.
authors.forename: Young Kyung
authors.initials: YK
authors.lastname: Bae
authors.affiliation: Department of Pathology, Soonchunhyang University Cheonan Hospital, Cheonan, Korea.
authors.forename: Soon Uk
authors.initials: SU
authors.lastname: Hong
authors.affiliation: Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Jene
authors.initials: J
authors.lastname: Choi
authors.affiliation: Department of Pathology, Inha University College of Medicine, Incheon, Korea.
authors.forename: Joon Mee
authors.initials: JM
authors.lastname: Kim
authors.affiliation: Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Kee-Taek
authors.initials: KT
authors.lastname: Jang
authors.affiliation: Department of Pathology, Inje University Sanggye Paik Hospital, Seoul, Korea.
authors.forename: Jung Yeon
authors.initials: JY
authors.lastname: Kim
authors.affiliation: Department of Pathology, CHA Bundang Medical Center, CHA University, Seongnam, Korea.
authors.forename: Gwang Il
authors.initials: GI
authors.lastname: Kim
authors.affiliation: Department of Pathology, Inje University College of Medicine, Busan, Korea.
authors.forename: Soo Jin
authors.initials: SJ
authors.lastname: Jung
authors.affiliation: Department of Pathology, Kyungpook National University School of Medicine, Daegu, Korea.
authors.forename: Ghilsuk
authors.initials: G
authors.lastname: Yoon
authors.affiliation: Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Seung-Mo
authors.initials: SM
authors.lastname: Hong
mesh_terms: D000230:Adenocarcinoma / Q000453:epidemiology* / Q000235:genetics / Q000473:pathology; D000328:Adult; D000368:Aged; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000453:epidemiology* / Q000235:genetics / Q000473:pathology; D053843:DNA Mismatch Repair / Q000235:genetics; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D015994:Incidence; D008297:Male; D042282:Microdissection; D008875:Middle Aged; D000070976:Mismatch Repair Endonuclease PMS2 / Q000235:genetics; D000070957:MutL Protein Homolog 1 / Q000235:genetics; D051718:MutS Homolog 2 Protein / Q000235:genetics; D016133:Polymerase Chain Reaction
chemical_list: 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: DNA mismatch repair; Lynch syndrome; hereditary nonpolyposis colorectal cancer syndrome; microsatellite instability; small intestinal adenocarcinoma