Role of dihydropyrimidine dehydrogenase and thymidylate synthase expression in immunohistochemistry of intrahepatic cholangiocarcinoma.
OBJECTIVE
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.
Nishi
Masaaki
M
Department of Surgery Department of Molecular and Environmental Pathology, Institute of Health Bioscience, The University of Tokushima, Kuramoto-cho, Tokushima, Japan.
Shimada
Mitsuo
M
Utsunomiya
Tohru
T
Morine
Yuji
Y
Imura
Satoru
S
Ikemoto
Tetsuya
T
Mori
Hiroki
H
Hanaoka
Jun
J
Bando
Yoshimi
Y