title: 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.affiliation: Department of Surgical Oncology, Osaka City University Graduate School of Medicine, Osaka, Japan. bunzo@med.osaka-cu.ac.jp
authors.forename: Bunzo
authors.initials: B
authors.lastname: Nakata
authors.forename: Masakazu
authors.initials: M
authors.lastname: Yashiro
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Nishioka
authors.forename: Makoto
authors.initials: M
authors.lastname: Aya
authors.forename: Shinobu
authors.initials: S
authors.lastname: Yamada
authors.forename: Chiemi
authors.initials: C
authors.lastname: Takenaka
authors.forename: Masaichi
authors.initials: M
authors.lastname: Ohira
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Ishikawa
authors.forename: Hiroji
authors.initials: H
authors.lastname: Nishino
authors.forename: Kenichi
authors.initials: K
authors.lastname: Wakasa
authors.forename: Shuichi
authors.initials: S
authors.lastname: Seki
authors.forename: Kosei
authors.initials: K
authors.lastname: Hirakawa
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D002288:Adenocarcinoma, Mucinous / Q000235:genetics*; D000368:Aged; D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics*; D002291:Carcinoma, Papillary / Q000235:genetics*; D002352:Carrier Proteins; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D019942:Genes, p16; D016158:Genes, p53; D006801:Humans; D007150:Immunohistochemistry; D015994:Incidence; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein; D009363:Neoplasm Proteins / Q000032:analysis / Q000235:genetics; D009687:Nuclear Proteins; D010190:Pancreatic Neoplasms / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000032:analysis / Q000235:genetics; D051901:Smad4 Protein; D015534:Trans-Activators / Q000235:genetics
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; C501486:MLH1 protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; C497796:SMAD4 protein, human; D051901:Smad4 Protein; D015534:Trans-Activators; C497172:MSH2 protein, human; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein