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, Toru Shimosegawa, Hideki OrikasaTomoo Watanabe, Kazuhiko Nishimura, Youji Harada, Toru Furukawa

研究成果: Article査読

63 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)1812-1817
ページ数6
ジャーナルAmerican Journal of Surgical Pathology
35
12
DOI
出版ステータスPublished - 2011 12

ASJC Scopus subject areas

  • 解剖学
  • 外科
  • 病理学および法医学

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