Assessment of clonality of multisegmental main duct intraductal papillary mucinous neoplasms of the pancreas based on GNAS mutation analysis

Koji Tamura, Takao Ohtsuka, Taketo Matsunaga, Hideyo Kimura, Yusuke Watanabe, Noboru Ideno, Teppei Aso, Tetsuyuki Miyazaki, Kenoki Ohuchida, Shunichi Takahata, Tetsuhide Ito, Yasuhiro Ushijima, Yoshinao Oda, Kazuhiro Mizumoto, Masao Tanaka

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Background Main duct intraductal papillary mucinous neoplasms (MD-IPMNs) may occur in 1 or multiple segments of the pancreatic duct. Unlike multifocal branch duct (BD)-IPMNs, the clonality of multisegmental MD-IPMNs remains unclear. GNAS mutations are common and specific for IPMNs, and mutational assessment might be useful to determine the clonality of IPMNs as well as to detect high-risk IPMN with distinct ductal adenocarcinoma (pancreatic ductal adenocarcinoma [PDAC]). Our aim was to clarify clonality using GNAS status in multisegmental MD-IPMNs. Methods We retrospectively reviewed the medical records of 70 patients with MD-IPMN. Histologic subtypes and KRAS/GNAS mutations were investigated, and the clonal relationships among multisegmental MD-IPMNs were assessed. Mutational analysis was performed using high-resolution melting analysis and subsequent Sanger/pyrosequencing. Results Thirteen patients had multiple synchronous and/or metachronous lesions. Seven of these 13 patients had multiple MD-IPMNs; 3 had multiple MD-IPMNs and distinct BD-IPMNs; 1 had multiple MD-IPMNs and a distinct PDAC; 1 had a solitary MD-IPMN, BD-IPMN, and PDAC; and 1 had a solitary MD-IPMN and PDAC. KRAS/GNAS mutations were consistent in 10 of 11 multisegmental MD-IPMNs, whereas MD-IPMNs, BD-IPMNs, and PDACs tended to show different mutational patterns. The frequency of malignant IPMNs was significantly higher in the multisegment cohort; malignant IPMNs constituted 90% (9/10) of the multiple cohort and 56% (32/57) of the solitary cohort (P =.04). Mutant GNAS was more frequently observed in the intestinal subtype (94%) than the others. Conclusion MD-IPMNs can be characterized by monoclonal skip progression. Close attention should be paid to the possible presence of skip areas during or after partial pancreatectomy.

Original languageEnglish
Pages (from-to)277-284
Number of pages8
JournalSurgery (United States)
Volume157
Issue number2
DOIs
Publication statusPublished - Feb 1 2015

All Science Journal Classification (ASJC) codes

  • Surgery

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