High expression of karyopherin-α2 and stathmin 1 is associated with proliferation potency and transformation in the bile duct and gall bladder epithelia in the cases of pancreaticobiliary maljunction

J Surg Oncol. 2016 Sep;114(4):462-8. doi: 10.1002/jso.24330. Epub 2016 Jun 23.

Abstract

Backgrounds and objectives: Pancreaticobiliary maljunction (PBM) may be associated with an increased frequency of gall bladder cancer with no bile duct dilation. Karyopherin-α2 (KPNA2) and stathmin 1 (STMN1) were reported to play important roles in carcinogenesis and cancer progression.

Methods: Fifteen patients with PBM who underwent surgical resection between 1999 and 2014 were included in this study. Using immunohistochemistry, we investigated the expression of p53, Ki-67, KPNA2, and STMN1 in normal biliary tract epithelium, hyperplastic epithelium, and cholangiocarcinoma (CC) tissues.

Results: Nuclear expression of KPNA2, p53, and Ki-67 expression was detected in hyperplastic epithelium and CC tissues. High KPNA2 expression was significantly associated with gender (P = 0.04), p53 nuclear accumulation (P = 0.00435), and Ki-67 expression (P = 0.0443) in the gall bladder and bile duct of PBM. On the other hand, STMN1 was only expressed in CC tissues and was not observed in normal bile duct and hyperplastic epithelia.

Conclusions: KPNA2 might be a useful marker of hyperplasia, dysplasia, and carcinogenicity in patients with PBM. STMN1 evaluation might be a cancer-specific marker for CC patients with PBM similar as that for other cancers. J. Surg. Oncol. 2016;114:462-468. © 2016 Wiley Periodicals, Inc.

Keywords: Op18; PBM; biliary tract cancer; inportin; stathmin 1.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Bile Duct Neoplasms / etiology
  • Bile Ducts / abnormalities*
  • Bile Ducts / pathology
  • Cell Proliferation
  • Female
  • Gallbladder / pathology*
  • Humans
  • Hyperplasia
  • Immunohistochemistry
  • Ki-67 Antigen / analysis
  • Male
  • Middle Aged
  • Pancreatic Ducts / abnormalities*
  • Stathmin / analysis*
  • Tumor Suppressor Protein p53 / analysis
  • alpha Karyopherins / analysis*

Substances

  • KPNA2 protein, human
  • Ki-67 Antigen
  • STMN1 protein, human
  • Stathmin
  • Tumor Suppressor Protein p53
  • alpha Karyopherins