Role of dihydropyrimidine dehydrogenase and thymidylate synthase expression in immunohistochemistry of intrahepatic cholangiocarcinoma

Masaaki Nishi; Mitsuo Shimada; Tohru Utsunomiya; Yuji Morine; Satoru Imura; Tetsuya Ikemoto; Hiroki Mori; Jun Hanaoka; Yoshimi Bando

doi:10.1111/j.1872-034X.2010.00722.x

Role of dihydropyrimidine dehydrogenase and thymidylate synthase expression in immunohistochemistry of intrahepatic cholangiocarcinoma

Hepatol Res. 2011 Jan;41(1):64-70. doi: 10.1111/j.1872-034X.2010.00722.x. Epub 2010 Sep 28.

Authors

Masaaki Nishi¹, Mitsuo Shimada, Tohru Utsunomiya, Yuji Morine, Satoru Imura, Tetsuya Ikemoto, Hiroki Mori, Jun Hanaoka, Yoshimi Bando

Affiliation

¹ Department of Surgery Department of Molecular and Environmental Pathology, Institute of Health Bioscience, The University of Tokushima, Kuramoto-cho, Tokushima, Japan.

PMID: 20880064
DOI: 10.1111/j.1872-034X.2010.00722.x

Abstract

Aims: Dihydropyrimidine dehydrogenase (DPD) and thymidylate synthase (TS) are key enzymes in the metabolism of 5-fluorouracil and have been implicated as possible prognostic markers for cancer patients. However, the clinical roles of DPD and TS in intrahepatic cholangiocarcinoma (IHCC) have not been investigated. The aim of this study was to clarify the clinicopathological role of DPD and TS expressions in IHCC.

Methods: Twenty-nine patients who had undergone hepatic resection for IHCC were enrolled in this study. Expressions of DPD and TS in the resected IHCC specimens were examined using anti-DPD or anti-TS antibody. The patients were divided into positive and negative groups according to DPD/TS expressions: DPD-positive group (n = 18) and DPD-negative group (n = 11)/TS-positive group (n = 14) and TS-negative group (n = 15). Clinicopathological factors were compared between the two groups.

Results: The overall survival rate was significantly lower in the DPD-negative group than in the DPD-positive group (1-year 36.4% vs. 77.4%, 3-year 18.2% vs. 43.0%; P < 0.05). The disease-free survival rate in the DPD-negative group tended to be lower than that in the DPD-positive group. The overall survival rate or disease-free survival rate did not appear to be associated with the TS-expression status. The Ki-67 labeling index in the DPD-negative group was significantly higher than that in the DPD-positive group (16.9 ± 3.2% vs.13.2 ± 3.3%; P < 0.05).

Conclusions: The negative DPD expression was significantly associated with the enhanced tumor cell proliferation and poorer prognosis in patients with IHCC. DPD expression is a potential prognostic indicator for IHCC.