Decreased p27Kip1 expression and cyclin D1 overexpression, alone and in combination, influence recurrence and survival of patients with resectable extrahepatic bile duct carcinoma

Authors

  • Ai-Min Hui M.D.,

    Corresponding author
    1. From the Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, University of Tokyo, Bunkyo-ku, Tokyo, Japan
    • Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan. fax: (81) 3-5684-3989
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  • Xing Cui,

    1. From the Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, University of Tokyo, Bunkyo-ku, Tokyo, Japan
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  • Masatoshi Makuuchi,

    1. From the Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, University of Tokyo, Bunkyo-ku, Tokyo, Japan
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  • Xin Li,

    1. From the Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, University of Tokyo, Bunkyo-ku, Tokyo, Japan
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  • Ya-Zhou Shi,

    1. From the Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, University of Tokyo, Bunkyo-ku, Tokyo, Japan
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  • Tadatoshi Takayama

    1. From the Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, University of Tokyo, Bunkyo-ku, Tokyo, Japan
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Abstract

This study was undertaken to identify potential abnormalities of p27Kip1 and cyclin D1 expression in extrahepatic bile duct carcinomas and to assess the prognostic significance of p27Kip1 and cyclin D1 levels for patients with this disease. Decreased p27Kip1 expression (<50% nuclei staining) and cyclin D1 overexpression (>5% nuclei staining) was observed immunohistochemically in 19 (56%) and 23 (68%) of the 34 tumors examined, respectively. Both decreased p27Kip1 and cyclin D1 overexpression were associated with relapse (P = .0005 for p27Kip1 and P = .0004 for cyclin D1). Kaplan-Meier curves showed that both decreased p27Kip1 and cyclin D1 overexpression correlate significantly with shortened survival rates (for p27Kip1, P = .0419 andP= .002 for overall and disease-free survival; for cyclin D1, P = .0392 andP= .0021 for overall and disease-free survival). Cox regression model analyses identified decreased p27Kip1 and cyclin D1 overexpression as independent markers predicting death from relapse (P = .0371, risk ratio: 3.891 for p27Kip1; P = .0429, risk ratio: 8.31 for cyclin D1). Decreased p27Kip1 was associated with cyclin D1 overexpression (P = .0202), and coincident abnormalities of the 2 proteins occurred in 16 of the 34 (47%) tumors, indicating that extrahepatic bile duct carcinoma progression may require synchronous dysfunction of p27Kip1 and cyclin D1 in about half of patients. Patients with tumors showing coincident abnormalities of p27Kip1 and cyclin D1 showed even more frequent recurrence than patients with an alteration in only 1 of the 2 proteins. In conclusion, decreased p27Kip1 expression and cyclin D1 overexpression, alone and in combination, predict poor prognosis in patients with resectable extrahepatic bile duct carcinoma

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