GNAS mutation is a frequent event in pancreatic intraductal papillary mucinous neoplasms and associated adenocarcinomas

• Published in: Virchows Archiv : an international journal of pathology Vol. 466; no. 6; pp. 665 - 674
• Main Authors: Hosoda, Waki, Sasaki, Eiichi, Murakami, Yoshiko, Yamao, Kenji, Shimizu, Yasuhiro, Yatabe, Yasushi
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.06.2015; Springer Nature B.V
• Subjects: Adenocarcinoma - genetics; Adenocarcinoma - mortality; Adenocarcinoma - pathology; Adenocarcinoma, Mucinous - genetics; Adenocarcinoma, Mucinous - mortality; Adenocarcinoma, Mucinous - pathology; Aged; Aged, 80 and over; Biomarkers, Tumor - genetics; Carcinoma, Pancreatic Ductal - genetics; Carcinoma, Pancreatic Ductal - mortality; Carcinoma, Pancreatic Ductal - pathology; Carcinoma, Papillary - genetics; Carcinoma, Papillary - mortality; Carcinoma, Papillary - pathology; Chromogranins; Cystadenoma - genetics; Cystadenoma - mortality; Cystadenoma - pathology; DNA Mutational Analysis; Female; Genotypes; GTP-Binding Protein alpha Subunits, Gs - genetics; Heterogeneity; Humans; Immunohistochemistry; Kaplan-Meier Estimate; Male; Medicine; Medicine & Public Health; Microdissection; Middle Aged; Mutation; Original Article; Pancreatic Neoplasms - genetics; Pancreatic Neoplasms - mortality; Pancreatic Neoplasms - pathology; Pathology; Reverse Transcriptase Polymerase Chain Reaction; Tumors; IPMN-associated adenocarcinoma; Mucinous; Pancreas; Tubular
• ISSN: 0945-6317; 1432-2307; 1432-2307
• DOI: 10.1007/s00428-015-1751-6

In contrast to pancreatic ductal adenocarcinomas (PDAs), intraductal papillary mucinous neoplasms (IPMNs) frequently harbour GNAS mutations. To characterise GNAS -mutated pancreatic carcinomas, we examined mutations of GNAS and KRAS in 290 pancreatic adenocarcinomas and 77 pancreatic intraepithelial neoplasias (PanINs). In 64 % (39/61) of IPMNs and 37 % (11/30) of IPMN-associated adenocarcinomas, a GNAS mutation was found. GNAS mutations were frequent (78 %, 7/9) in mucinous carcinomas, with or without associated IPMN. In contrast, GNAS mutations were rarely observed in PDAs (1 %, 1/88) and PanINs (3 %, 2/77), and not at all in mucinous cystic neoplasms (MCNs) (0/10), neuroendocrine neoplasms (0/52), acinar cell neoplasms (0/16), serous cystadenomas (0/10), and solid-pseudopapillary neoplasms (0/14). We found GNAS mutations in 55/91 IPMNs with or without associated invasive carcinoma, solely in intestinal-type (78 %, 21/27) and gastric-type (62 %, 34/55) IPMNs. Of the IPMN-associated adenocarcinomas, mucinous-subtype tumours harboured GNAS mutations more frequently (83 %, 5/6) than tubular-subtype tumours (25 %, 6/24) ( p  = 0.02). We separately analysed GNAS in the adenocarcinoma and the IPMN component in the IPMN-associated adenocarcinomas. In all mucinous-subtype tumours, the two components exhibited identical genotypes. In contrast, the two components in 8 of 24 tubular-subtype tumours exhibited different genotypes, indicating intratumour heterogeneity. In conclusion, mucinous carcinomas with or without associated IPMN as well as IPMNs frequently harbour a GNAS mutation, reinforcing the notion that these constitute a spectrum of pancreatic tumours. Clinically and pathologically, these tumours are associated, but GNAS mutation sheds further light on this spectrum.