Very low incidence of microsatellite instability in intraductal papillary-mucinous neoplasm of the pancreas

Int J Cancer. 2002 Dec 20;102(6):655-9. doi: 10.1002/ijc.10771.

Abstract

Intraductal papillary-mucinous carcinoma (IPMC) of the pancreas, a new entity of pancreatic cancer with a favorable prognosis, has shown a gradual increase in the number of reported cases. Patients with high-frequency microsatellite instability (MSI-H) tumors have been shown to survive longer than those with low-frequency MSI (MSI-L) or microsatellite stable (MSS) tumors in colorectal and gastric cancer. We investigated whether MSI-H in patients with IPMC can contribute to a good prognosis. The formalin-fixed paraffin-embedded tumors and surrounding normal pancreatic tissues from 10 patients with IPMCs and 16 with intraductal papillary-mucinous adenomas (IPMAs) were provided for DNA extraction after microdissection. Polymerase chain reaction (PCR) was carried out using 8 microsatellite primer marker sets. The mixed PCR samples were analyzed using a genetic analyzer. MSI-H was determined by assessment of microsatellite variations in 3 or more of the 8 tested markers. Immunohistochemical staining of the MSI-responsible proteins hMLH1 and hMSH2 was conducted for both the IPMC and IPMA samples. Ten percent of IPMC harbored MSI-H tumors, whereas no MSI-H tumors were detected in the IPMAs. Thirty percent of IPMC tumors and 25% of IPMA tumors showed MSI-L. All IPMCs and IPMAs showed normal expression of both hMLH1 and hMSH2. MSI-H and loss of hMLH1 and hMSH2 are very rare events in both IPMCs and IPMAs. We conclude that a good prognosis for patients with IPMC is not associated with MSI-H.

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Adenocarcinoma, Mucinous / genetics*
  • Aged
  • Carcinoma, Pancreatic Ductal / genetics*
  • Carcinoma, Papillary / genetics*
  • Carrier Proteins
  • DNA-Binding Proteins / genetics
  • Female
  • Genes, p16
  • Genes, p53
  • Humans
  • Immunohistochemistry
  • Incidence
  • Male
  • Microsatellite Repeats*
  • Middle Aged
  • MutL Protein Homolog 1
  • MutS Homolog 2 Protein
  • Neoplasm Proteins / analysis
  • Neoplasm Proteins / genetics
  • Nuclear Proteins
  • Pancreatic Neoplasms / genetics*
  • Proto-Oncogene Proteins / analysis
  • Proto-Oncogene Proteins / genetics
  • Smad4 Protein
  • Trans-Activators / genetics

Substances

  • Adaptor Proteins, Signal Transducing
  • Carrier Proteins
  • DNA-Binding Proteins
  • MLH1 protein, human
  • Neoplasm Proteins
  • Nuclear Proteins
  • Proto-Oncogene Proteins
  • SMAD4 protein, human
  • Smad4 Protein
  • Trans-Activators
  • MSH2 protein, human
  • MutL Protein Homolog 1
  • MutS Homolog 2 Protein