HNPCC-associated small bowel cancer: Clinical and molecular characteristics

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. His...

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Veröffentlicht in:Gastroenterology (New York, N.Y. 1943) N.Y. 1943), 2005-03, Vol.128 (3), p.590-599
Hauptverfasser: Schulmann, Karsten, Brasch, Frank E., Kunstmann, Erdmute, Engel, Christoph, Pagenstecher, Constanze, Vogelsang, Holger, Krüger, Stefan, Vogel, Tilman, Knaebel, Hanns-Peter, Rüschoff, Josef, Hahn, Stephan A., Knebel-Doeberitz, Magnus V., Moeslein, Gabriela, Meltzer, Stephen J., Schackert, Hans K., Tympner, Christiane, Mangold, Elisabeth, Schmiegel, Wolff
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Sprache:eng
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Zusammenfassung: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.
ISSN:0016-5085
1528-0012
DOI:10.1053/j.gastro.2004.12.051