%0 Journal Article %1 Schulmann.2005 %A Schulmann, Karsten %A Brasch, Frank E. %A Kunstmann, Erdmute %A Engel, Christoph %A Pagenstecher, Constanze %A Vogelsang, Holger %A Krüger, Stefan %A Vogel, Tilman %A Knaebel, Hanns-Peter %A Rüschoff, Josef %A Hahn, Stephan A. %A Knebel-Doeberitz, Magnus V. %A Moeslein, Gabriela %A Meltzer, Stephen J. %A Schackert, Hans K. %A Tympner, Christiane %A Mangold, Elisabeth %A Schmiegel, Wolff %D 2005 %J Gastroenterology %K IMISE-Publikationen %N 3 %P 590–599 %T HNPCC-associated small bowel cancer: clinical and molecular characteristics %V 128 %X 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.

@article{Schulmann.2005, 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.}, added-at = {2014-10-15T15:04:25.000+0200}, author = {Schulmann, Karsten and Brasch, Frank E. and Kunstmann, Erdmute and Engel, Christoph and Pagenstecher, Constanze and Vogelsang, Holger and Krüger, Stefan and Vogel, Tilman and Knaebel, Hanns-Peter and Rüschoff, Josef and Hahn, Stephan A. and Knebel-Doeberitz, Magnus V. and Moeslein, Gabriela and Meltzer, Stephen J. and Schackert, Hans K. and Tympner, Christiane and Mangold, Elisabeth and Schmiegel, Wolff}, biburl = {https://www.bibsonomy.org/bibtex/2d26574a171a9aacfae42bafe96b7186c/drtester}, interhash = {8209a3f58bcde78ebbc8b20859836a81}, intrahash = {d26574a171a9aacfae42bafe96b7186c}, journal = {Gastroenterology}, keywords = {IMISE-Publikationen}, number = 3, pages = {590–599}, timestamp = {2014-12-03T00:09:13.000+0100}, title = {HNPCC-associated small bowel cancer: clinical and molecular characteristics}, volume = 128, year = 2005 }