HNPCC-associated small bowel cancer: clinical and molecular characteristics
- PMID: 15765394
- DOI: 10.1053/j.gastro.2004.12.051
HNPCC-associated small bowel cancer: clinical and molecular characteristics
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.
Similar articles
-
Lynch syndrome (hereditary nonpolyposis colorectal cancer) diagnostics.J Natl Cancer Inst. 2007 Feb 21;99(4):291-9. doi: 10.1093/jnci/djk051. J Natl Cancer Inst. 2007. PMID: 17312306
-
Atypical HNPCC owing to MSH6 germline mutations: analysis of a large Dutch pedigree.J Med Genet. 2001 May;38(5):318-22. doi: 10.1136/jmg.38.5.318. J Med Genet. 2001. PMID: 11333868 Free PMC article.
-
Use of molecular tumor characteristics to prioritize mismatch repair gene testing in early-onset colorectal cancer.J Clin Oncol. 2005 Sep 20;23(27):6524-32. doi: 10.1200/JCO.2005.04.671. Epub 2005 Aug 22. J Clin Oncol. 2005. PMID: 16116158
-
Hereditary nonpolyposis colorectal cancer: diagnostic strategies and their implications.Evid Rep Technol Assess (Full Rep). 2007 May;(150):1-180. Evid Rep Technol Assess (Full Rep). 2007. PMID: 17764220 Free PMC article. Review.
-
Identification of HNPCC by molecular analysis of colorectal and endometrial tumors.Dis Markers. 2004;20(4-5):207-13. doi: 10.1155/2004/391039. Dis Markers. 2004. PMID: 15528786 Free PMC article. Review.
Cited by
-
Effectiveness of a dedicated small bowel neoplasia screening program by capsule endoscopy in Lynch syndrome: 5 years results from a tertiary care center.Therap Adv Gastroenterol. 2020 Jul 29;13:1756284820934314. doi: 10.1177/1756284820934314. eCollection 2020. Therap Adv Gastroenterol. 2020. PMID: 32774463 Free PMC article.
-
Current Immune Checkpoint Inhibitor Genetic Biomarker Exploration in Gastrointestinal Tumors.Cancers (Basel). 2022 Sep 30;14(19):4804. doi: 10.3390/cancers14194804. Cancers (Basel). 2022. PMID: 36230726 Free PMC article. Review.
-
DROSHA-Dependent miRNA and AIM2 Inflammasome Activation in Idiopathic Pulmonary Fibrosis.Int J Mol Sci. 2020 Feb 28;21(5):1668. doi: 10.3390/ijms21051668. Int J Mol Sci. 2020. PMID: 32121297 Free PMC article. Review.
-
Epidemiology of cancer of the small intestine.World J Gastrointest Oncol. 2011 Mar 15;3(3):33-42. doi: 10.4251/wjgo.v3.i3.33. World J Gastrointest Oncol. 2011. PMID: 21461167 Free PMC article.
-
Genetic syndromes predisposing to pediatric brain tumors.Neurooncol Pract. 2021 Feb 13;8(4):375-390. doi: 10.1093/nop/npab012. eCollection 2021 Aug. Neurooncol Pract. 2021. PMID: 34277017 Free PMC article. Review.
Publication types
MeSH terms
LinkOut - more resources
Full Text Sources
Research Materials
Miscellaneous