HNPCC-associated small bowel cancer: Clinical and molecular characteristics

Karsten Schulmann, Frank E. Brasch, Erdmute Kunstmann, Christoph Engel, Constanze Pagenstecher, Holger Vogelsang, Stefan Krüger, Tilman Vogel, Hanns Peter Knaebel, Josef Rüschoff, Stephan A. Hahn, Magnus V. Knebel-Doeberitz, Gabriela Moeslein, Stephen Meltzer, Hans K. Schackert, Christiane Tympner, Elisabeth Mangold, Wolff Schmiegel

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)590-599
Number of pages10
JournalGastroenterology
Volume128
Issue number3
DOIs
StatePublished - Mar 2005
Externally publishedYes

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Intestinal Neoplasms
Hereditary Nonpolyposis Colorectal Neoplasms
Microsatellite Instability
DNA Mismatch Repair
Frameshift Mutation
Germ-Line Mutation
Neoplasms
Duodenum
Endoscopy
Stomach Neoplasms
Proteins
Immunohistochemistry
Mutation
Growth

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Schulmann, K., Brasch, F. E., Kunstmann, E., Engel, C., Pagenstecher, C., Vogelsang, H., ... Schmiegel, W. (2005). HNPCC-associated small bowel cancer: Clinical and molecular characteristics. Gastroenterology, 128(3), 590-599. https://doi.org/10.1053/j.gastro.2004.12.051

HNPCC-associated small bowel cancer : Clinical and molecular characteristics. / 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; Schackert, Hans K.; Tympner, Christiane; Mangold, Elisabeth; Schmiegel, Wolff.

In: Gastroenterology, Vol. 128, No. 3, 03.2005, p. 590-599.

Research output: Contribution to journalArticle

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, S, Schackert, HK, Tympner, C, Mangold, E & Schmiegel, W 2005, 'HNPCC-associated small bowel cancer: Clinical and molecular characteristics', Gastroenterology, vol. 128, no. 3, pp. 590-599. https://doi.org/10.1053/j.gastro.2004.12.051
Schulmann K, Brasch FE, Kunstmann E, Engel C, Pagenstecher C, Vogelsang H et al. HNPCC-associated small bowel cancer: Clinical and molecular characteristics. Gastroenterology. 2005 Mar;128(3):590-599. https://doi.org/10.1053/j.gastro.2004.12.051
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 ; Schackert, Hans K. ; Tympner, Christiane ; Mangold, Elisabeth ; Schmiegel, Wolff. / HNPCC-associated small bowel cancer : Clinical and molecular characteristics. In: Gastroenterology. 2005 ; Vol. 128, No. 3. pp. 590-599.
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AU - Schulmann, Karsten

AU - Brasch, Frank E.

AU - Kunstmann, Erdmute

AU - Engel, Christoph

AU - Pagenstecher, Constanze

AU - Vogelsang, Holger

AU - Krüger, Stefan

AU - Vogel, Tilman

AU - Knaebel, Hanns Peter

AU - Rüschoff, Josef

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AU - Knebel-Doeberitz, Magnus V.

AU - Moeslein, Gabriela

AU - Meltzer, Stephen

AU - Schackert, Hans K.

AU - Tympner, Christiane

AU - Mangold, Elisabeth

AU - Schmiegel, Wolff

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