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Int J Clin Exp Pathol 2011;4(4):363-370

Original Article
Prognostic significance of NQO1 expression in intrahepatic cholangiocarcinoma

Toshifumi Wakai, Yoshio Shirai, Jun Sakata, Yasunobu Matsuda1, Pavel V. Korita2, Masaaki Takamura1, Yoichi Ajioka2, Katsuyoshi

Division of Digestive and General Surgery, Division of Gastroenterology and Hepatology, and Division of Molecular and Diagnostic Pathology,
Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan

Received March 15, 2011; accepted March 28, 2011; Epub April 10, 2011; published April 30, 2011

Abstract: This study aimed to evaluate the association between the immunohistochemical expression of NAD(P)H:quinone oxidoreductase-1
(NQO1) and nuclear factor erythroid 2-related factor 2 (Nrf2) in resected specimens of intrahepatic cholangiocarcinoma (ICC) and to elucidate
the prognostic value of NQO1 and Nrf2 expression. A retrospective analysis was conducted of 34 consecutive patients who underwent surgical
resection for ICC. Immunohistochemistry of the resected specimens was conducted using each of the following primary monoclonal
antibodies against NQO1 and Nrf2. Of the 34 patients, 23 were classified as having tumors with NQO1-positive expression and 11 had tumors
with loss of NQO1 expression, whereas 22 patients had tumors with Nrf2-positive expression and 12 had tumors with loss of Nrf2 expression.
NQO1 expression showed a positive association with Nrf2 expression (p=0.005). Loss of NQO1 expression was more frequent in tumor
specimens that were moderately or poorly differentiated (11/26; 42%) than in well-differentiated tumors (0/8; 0%; p=0.034). Post-resection
survival was significantly worse in patients with tumors with loss of NQO1 expression than in patients with NQO1-positive tumors (cumulative
5-year survival rate of 0% and 51%, respectively; p=0.005). Nrf2 expression was not associated with survival after resection (p=0.287). The Cox
proportional hazards regression analysis revealed that lymph node involvement (p<0.001) and loss of NQO1 expression (p<0.001) had an
independent adverse effect on survival. Loss of NQO1 expression reflects dedifferentiation and thus indicates a poor prognosis for patients
undergoing resection for ICC. (IJCEP1103007).

Keywords: NAD(P)H:quinone oxidoreductase-1 (NQO1), intrahepatic cholangiocarcinoma, nuclear factor erythroid 2-related factor 2 (Nrf2),
surgical resection, prognosis

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Address all correspondence to:
Toshifumi Wakai, MD, PhD
Division of Digestive and General Surgery
Niigata University Graduate School of Medical and Dental Sciences
1-757 Asahimachi-dori, Chuo-ku
Niigata 951-8510, Japan.
Tel: +81-25-227-2228, Fax: +81-25-227-0779