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.