HNPCC-associated small bowel cancer: clinical and molecular characteristics

Gastroenterology. 2005 Mar;128(3):590-9. doi: 10.1053/j.gastro.2004.12.051.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Colorectal Neoplasms, Hereditary Nonpolyposis / genetics*
  • Colorectal Neoplasms, Hereditary Nonpolyposis / metabolism
  • Colorectal Neoplasms, Hereditary Nonpolyposis / mortality
  • Colorectal Neoplasms, Hereditary Nonpolyposis / pathology*
  • Duodenal Neoplasms / genetics
  • Duodenal Neoplasms / pathology
  • Female
  • Frameshift Mutation
  • Germ-Line Mutation
  • Humans
  • Immunohistochemistry
  • Intestinal Neoplasms / genetics*
  • Intestinal Neoplasms / metabolism
  • Intestinal Neoplasms / mortality
  • Intestinal Neoplasms / pathology*
  • Intestine, Small* / pathology
  • Male
  • Microsatellite Repeats
  • Middle Aged