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Title:

HNPCC-associated small bowel cancer: clinical and molecular characteristics.

Document type:
Journal Article
Author(s):
Schulmann, K; Brasch, FE; Kunstmann, E; Engel, C; Pagenstecher, C; Vogelsang, H; Krüger, S; Vogel, T; Knaebel, HP; Rüschoff, J; Hahn, SA; Knebel-Doeberitz, MV; Moeslein, G; Meltzer, SJ; Schackert, HK; Tympner, C; Mangold, E; Schmiegel, W
Abstract:
BACKGROUND & AIMS: 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.
Journal title abbreviation:
Gastroenterology
Year:
2005
Journal volume:
128
Journal issue:
3
Pages contribution:
590-9
Language:
eng
Pubmed ID:
http://view.ncbi.nlm.nih.gov/pubmed/15765394
Print-ISSN:
0016-5085
TUM Institution:
Chirurgische Klinik und Poliklinik
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