title: HNPCC-associated small bowel cancer: clinical and molecular characteristics.
abstract: OBJECTIVE
  The risk for small bowel cancer (SBC) is significantly increased in hereditary nonpolyposis colorectal cancer (HNPCC). HNPCC-associated SBCs are poorly characterized.
  
  
  METHODS
  Thirty-two SBCs were characterized according to clinical, pathologic, and germline mutation data. Histomorphologic characteristics, microsatellite instability (MSI) testing, mismatch repair (MMR) protein expression, and frameshift mutations of 7 coding mononucleotide repeats were investigated in 17 SBCs.
  
  
  RESULTS
  Median age at diagnosis was 39 years. Fifty percent of SBCs were located in the duodenum. The Amsterdam criteria were fulfilled in 50% of patients; 45% of patients had no personal history of previous malignancies. Two patients had a positive family history for SBC. Pathogenic germline mutations were identified in 81%; high MSI was detected in 95% and loss of MMR protein expression in 89% of cases. TGFBR2 , BAX , MSH3 , MSH6 , ACVR2 , AIM2 , and SEC63 frameshift mutations were detected in 69%, 59%, 59%, 35%, 82%, 56%, and 56%, respectively. An expansive growth pattern of the tumor border and an intense intratumoral lymphocytic infiltrate were present in 75%, respectively.
  
  
  CONCLUSIONS
  HNPCC-associated SBC often manifests at a young age and may be the first disease manifestation. Endoscopy may detect 50% of tumors. Considering recent data on gastric cancer, we propose endoscopic screening of mutation carriers starting at 30 years of age because clinical criteria cannot define a high-risk group. In addition, our study shows that histopathologic criteria, MSI, and MMR immunohistochemistry are often similar to these features in HNPCC.
authors.affiliation: Department of Medicine, Knappschaftskrankenhaus, Ruhr-University Bochum, Bochum, Germany.
authors.forename: Karsten
authors.initials: K
authors.lastname: Schulmann
authors.forename: Frank E
authors.initials: FE
authors.lastname: Brasch
authors.forename: Erdmute
authors.initials: E
authors.lastname: Kunstmann
authors.forename: Christoph
authors.initials: C
authors.lastname: Engel
authors.forename: Constanze
authors.initials: C
authors.lastname: Pagenstecher
authors.forename: Holger
authors.initials: H
authors.lastname: Vogelsang
authors.forename: Stefan
authors.initials: S
authors.lastname: Krüger
authors.forename: Tilman
authors.initials: T
authors.lastname: Vogel
authors.forename: Hanns-Peter
authors.initials: HP
authors.lastname: Knaebel
authors.forename: Josef
authors.initials: J
authors.lastname: Rüschoff
authors.forename: Stephan A
authors.initials: SA
authors.lastname: Hahn
authors.forename: Magnus V
authors.initials: MV
authors.lastname: Knebel-Doeberitz
authors.forename: Gabriela
authors.initials: G
authors.lastname: Moeslein
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Meltzer
authors.forename: Hans K
authors.initials: HK
authors.lastname: Schackert
authors.forename: Christiane
authors.initials: C
authors.lastname: Tympner
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Mangold
authors.forename: Wolff
authors.initials: W
authors.lastname: Schmiegel
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D004379:Duodenal Neoplasms / Q000235:genetics / Q000473:pathology; D005260:Female; D016368:Frameshift Mutation; D018095:Germ-Line Mutation; D006801:Humans; D007150:Immunohistochemistry; D007414:Intestinal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D007421:Intestine, Small / Q000473:pathology; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged