title: Clinical significance of GNAS mutation in intraductal papillary mucinous neoplasm of the pancreas with concomitant pancreatic ductal adenocarcinoma.
abstract: OBJECTIVE
  The aims of this study were to investigate the GNAS mutational status in pancreatic intraductal papillary mucinous neoplasm (IPMN) with and without distinct pancreatic ductal adenocarcinoma (PDAC) and to evaluate the significance of GNAS analysis using duodenal fluid (DF) in patients with IPMN.
  
  
  METHODS
  The clinicopathologic features of 110 patients with IPMN including 16 with distinct PDAC were reviewed. The GNAS status in the IPMN tissue and 23 DF specimens was assessed by sensitive mutation scanning methods.
  
  
  RESULTS
  The GNAS mutation rate in IPMN with distinct PDAC was significantly lower than that in IPMN without PDAC (4/16, 25%, vs 61/94, 65%; P = 0.0047). By multivariate analysis, GNAS wild-type and gastric type IPMNs were significantly associated with distinct PDAC. Of 45 GNAS wild-type IPMNs, 10 (43%) of 23 gastric type IPMNs had distinct PDAC, whereas only 2 (9%) of 22 non-gastric type IPMNs had distinct PDAC (P = 0.017). The GNAS status in DF was consistent with that in tissue in 21 (91%) of 23 patients.
  
  
  CONCLUSIONS
  Distinct PDACs frequently develop in the pancreas with gastric type IPMN without GNAS mutations. Duodenal fluid DNA test would predict the GNAS status of IPMN, whereas the detection of the gastric subtype using noninvasive test remains to be determined.
authors.affiliation: From the *Departments of Surgery and Oncology, and †Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Noboru
authors.initials: N
authors.lastname: Ideno
authors.forename: Takao
authors.initials: T
authors.lastname: Ohtsuka
authors.forename: Taketo
authors.initials: T
authors.lastname: Matsunaga
authors.forename: Hideyo
authors.initials: H
authors.lastname: Kimura
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Watanabe
authors.forename: Koji
authors.initials: K
authors.lastname: Tamura
authors.forename: Teppei
authors.initials: T
authors.lastname: Aso
authors.forename: Shinichi
authors.initials: S
authors.lastname: Aishima
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Miyasaka
authors.forename: Kenoki
authors.initials: K
authors.lastname: Ohuchida
authors.forename: Junji
authors.initials: J
authors.lastname: Ueda
authors.forename: Shunichi
authors.initials: S
authors.lastname: Takahata
authors.forename: Yoshinao
authors.initials: Y
authors.lastname: Oda
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Mizumoto
authors.forename: Masao
authors.initials: M
authors.lastname: Tanaka
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics*; D001706:Biopsy; D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics* / Q000378:metabolism / Q000401:mortality; D002864:Chromogranins; D004252:DNA Mutational Analysis / Q000379:methods*; D004386:Duodenum / Q000378:metabolism; D005260:Female; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000235:genetics*; D006801:Humans; D007419:Intestinal Secretions / Q000737:chemistry / Q000378:metabolism; D053208:Kaplan-Meier Estimate; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009154:Mutation; D018193:Neoplasms, Complex and Mixed / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D018297:Neoplasms, Cystic, Mucinous, and Serous / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D011237:Predictive Value of Tests; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D012307:Risk Factors; D018631:ras Proteins / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; D002864:Chromogranins; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; C406732:GNAS protein, human; D019205:GTP-Binding Protein alpha Subunits, Gs; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins