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 language | English (US) |
|---|---|
| Pages (from-to) | 590-599 |
| Number of pages | 10 |
| Journal | Gastroenterology |
| Volume | 128 |
| Issue number | 3 |
| DOIs | |
| State | Published - Mar 2005 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Gastroenterology
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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 journal › Article
}
TY - JOUR
T1 - HNPCC-associated small bowel cancer
T2 - Clinical and molecular characteristics
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
AU - Hahn, Stephan A.
AU - Knebel-Doeberitz, Magnus V.
AU - Moeslein, Gabriela
AU - Meltzer, Stephen
AU - Schackert, Hans K.
AU - Tympner, Christiane
AU - Mangold, Elisabeth
AU - Schmiegel, Wolff
PY - 2005/3
Y1 - 2005/3
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=20244387702&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=20244387702&partnerID=8YFLogxK
U2 - 10.1053/j.gastro.2004.12.051
DO - 10.1053/j.gastro.2004.12.051
M3 - Article
C2 - 15765394
AN - SCOPUS:20244387702
VL - 128
SP - 590
EP - 599
JO - Gastroenterology
JF - Gastroenterology
SN - 0016-5085
IS - 3
ER -