Fumiyoshi Saito1,2, Kenichiro Araki1,2, Takehiko Yokobori3, Norihiro Ishii1,2, Mariko Tsukagoshi1,2, Akira Watanabe1,2, Norio Kubo1,2, Bolag Altan1, Ken Shirabe2, Hiroyuki Kuwano1. 1. Department of General Surgical Science, Graduate School of Medicine, Gunma University, Showamachi, Maebashi, Gunma, Japan. 2. Department of Hepatobiliary and Pancreatic Surgery, Graduate School of Medicine, Gunma University, Maebashi, Gunma, Japan. 3. Department of Molecular Pharmacology and Oncology, Graduate School of Medicine, Gunma University, Maebashi, Gunma, Japan.
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.
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.