HNPCC-associated small bowel cancer: clinical and molecular characteristics.
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.
Schulmann
Karsten
K
Department of Medicine, Knappschaftskrankenhaus, Ruhr-University Bochum, Bochum, Germany.
Brasch
Frank E
FE
Kunstmann
Erdmute
E
Engel
Christoph
C
Pagenstecher
Constanze
C
Vogelsang
Holger
H
Krüger
Stefan
S
Vogel
Tilman
T
Knaebel
Hanns-Peter
HP
Rüschoff
Josef
J
Hahn
Stephan A
SA
Knebel-Doeberitz
Magnus V
MV
Moeslein
Gabriela
G
Meltzer
Stephen J
SJ
Schackert
Hans K
HK
Tympner
Christiane
C
Mangold
Elisabeth
E
Schmiegel
Wolff
W
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