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

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.

• Authors: Bunzo Nakata, Masakazu Yashiro, Nobuaki Nishioka, Makoto Aya, Shinobu Yamada, Chiemi Takenaka, Masaichi Ohira, Tetsuro Ishikawa, Hiroji Nishino, Kenichi Wakasa, Shuichi Seki, Kosei Hirakawa
• Journal: International journal of cancer (Int J Cancer) Vol. 102 Issue 6 Pg. 655-9 (Dec 20 2002) ISSN: 0020-7136 [Print] United States
• PMID: 12448010 (Publication Type: Journal Article)
• Copyright: Copyright 2002 Wiley-Liss, Inc.

Chemical References

• 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

Topics

• 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, genetics)
• Nuclear Proteins
• Pancreatic Neoplasms (genetics)
• Proto-Oncogene Proteins (analysis, genetics)
• Smad4 Protein
• Trans-Activators (genetics)