Molecular characteristics and biological behaviours of the oncocytic and pancreatobiliary subtypes of intraductal papillary mucinous neoplasms

Hong D. Xiao, Hiroshi Yamaguchi, Dora Dias-Santagata, Yuko Kuboki, Sara Akhavanfard, Takashi Hatori, Masakazu Yamamoto, Keiko Shiratori, Makio Kobayashi, Michio Shimizu, Carlos Fernandez-Del Castillo, Mari Mino-Kenudson, Toru Furukawa

Research output: Contribution to journalArticlepeer-review

40 Citations (Scopus)

Abstract

Intraductal papillary mucinous neoplasm (IPMN) consists of four epithelial subtypes. Of those, pancreatobiliary and oncocytic types are recently recognized and relatively uncommon, and usually exhibit high-grade dysplasia. The biological properties and molecular characteristics of these two types have not been well documented. The few molecular studies of the oncocytic type showed absence of KRAS mutations commonly seen in the other subtypes, raising the possibility that the oncocytic type is distinct from the other subtypes. Thus, we examined clinicopathological features and molecular alterations of the two subtypes. The study cohort consisted of 12 pancreatobiliary and 18 oncocytic IPMN cases. KRAS, BRAF, and PIK3CA mutations and TP53, SMAD4, and β-catenin expression were analysed, and the results of molecular and clinicopathological profiles were compared between the two subtypes. KRAS mutations were identified in the oncocytic type, but less frequently than the pancreatobiliary type (17% versus 58%, p = 0.048). BRAF mutation was found in a single oncocytic tumour, and no PIK3CA mutations were seen in any of the study cohort. TP53 overexpression was less frequent in the oncocytic type than in the pancreatobiliary type (11% versus 58%, p = 0.013). Invasive components were present in 50% of the oncocytic and 92% of the pancreatobiliary types, with lymph node metastasis more frequently seen in the latter, corresponding to better outcomes in the former (5-year survival rates: 93% versus 32%, p = 0.014). Our demonstration of KRAS and BRAF mutations in the oncocytic-type IPMN supports a role for the activation of the RAS-MAPK pathway in this tumour type. However, the less frequent TP53 overexpression associated with the significantly lower rates of invasion and nodal disease in the oncocytic type correlates with better outcomes compared to the pancreatobiliary type.

Original languageEnglish
Pages (from-to)508-516
Number of pages9
JournalJournal of Pathology
Volume224
Issue number4
DOIs
Publication statusPublished - 2011 Aug
Externally publishedYes

Keywords

  • cystic
  • intraductal papillary mucinous neoplasm
  • molecular
  • oncocytic
  • pancreas
  • pancreatobiliary
  • survival

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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