Somatic mutations in PIK3CA and activation of AKT in intraductal tubulopapillary neoplasms of the pancreas

Hiroshi Yamaguchi, Yuko Kuboki, Takashi Hatori, Masakazu Yamamoto, Keiko Shiratori, Shunji Kawamura, Makio Kobayashi, Michio Shimizu, Shinichi Ban, Isamu Koyama, Morihiro Higashi, Nobuhiro Shin, Kazuyuki Ishida, Takanori Morikawa, Fuyuhiko Motoi, Michiaki Unno, Atsushi Kanno, Kennichi Satoh, Tooru Shimosegawa, Hideki OrikasaTomoo Watanabe, Kazuhiko Nishimura, Youji Harada, Toru Furukawa

Research output: Contribution to journalArticlepeer-review

58 Citations (Scopus)

Abstract

Intraductal tubulopapillary neoplasm (ITPN) is a recently recognized rare variant of intraductal neoplasms of the pancreas. Molecular aberrations underlying the neoplasm remain unknown. We investigated somatic mutations in PIK3CA, PTEN, AKT1, KRAS, and BRAF. We also investigated aberrant expressions of phosphorylated AKT, phosphatase and tensin homolog (PTEN), tumor protein 53 (TP53), SMAD4, and CTNNB1 in 11 cases of ITPNs and compared these data with those of 50 cases of intraductal papillary mucinous neoplasm (IPMN), another distinct variant of pancreatic intraductal neoplasms. Mutations in PIK3CA were found in 3 of 11 ITPNs but not in IPMNs (P=0.005; Fisher exact test). In contrast, mutations in KRAS were found in none of the ITPNs but were found in 26 of the 50 IPMNs (P=0.001; Fisher exact test). PIK3CA mutations were associated with strong expression of phosphorylated AKT (P<0.001; the Mann-Whitney U test). Moreover, the expression of phosphorylated AKT was apparent in most ITPNs but only in a few IPMNs (P<0.001; the Mann-Whitney U test). Aberrant expressions of TP53, SMAD4, and CTNNB1 were not statistically different between these neoplasms. Mutations in PIK3CA and the expression of phosphorylated AKT were not associated with age, sex, tissue invasion, and patients' prognosis in ITPNs. These results indicate that activation of the phosphatidylinositol 3-kinase pathway may play a crucial role in ITPNs but not in IPMNs. In contrast, the mutation in KRAS seems to play a major role in IPMNs but not in ITPNs. The activated phosphatidylinositol 3-kinase pathway may be a potential target for molecular diagnosis and therapy of ITPNs.

Original languageEnglish
Pages (from-to)1812-1817
Number of pages6
JournalAmerican Journal of Surgical Pathology
Volume35
Issue number12
DOIs
Publication statusPublished - 2011 Dec

Keywords

  • AKT
  • KRAS
  • PTEN
  • pancreatic cancer
  • phosphatidylinositol 3 kinase

ASJC Scopus subject areas

  • Anatomy
  • Surgery
  • Pathology and Forensic Medicine

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