1. ¹Faculty of Medicine, Second Department of Surgery, Kagawa University, 1750-1, Miki-cho, Kita-gun, Kagawa 761-0793, Japan
2. ²Faculty of Medicine, Department of Pathology and Host Defense, Kagawa University, Kagawa, Japan
3. ³Faculty of Medicine, Department of Thoracic Surgery, Kyoto University, 54, Shogoin-kawahara-cho, Sakyo-ku, Kyoto, 606-8397, Japan
4. ⁴Pathology Optimal Medication Research Laboratory, Taiho Pharmaceutical Co. Ltd, 224-2, Hiraishi-Ebisuno, Kawauchi-cho, Tokushima-shi, Tokushima 771-0132, Japan

Correspondence: Dr C Huang, E-mail: chuang@kms.ac.jp

Received 8 March 2006; Revised 26 June 2006; Accepted 29 June 2006; Published online 1 August 2006.

Abstract

The sensitivity to 5-fluorouracil (5-FU) has been reported to be associated with target molecule thymidylate synthase (TS), fluoropyrimidine-metabolising enzymes such as orotate phosphoribosyltransferase (OPRT), and dihydropyrimidine dehydrogenase (DPD). We performed an immunohistochemical study on the clinical significance of TS, OPRT, and DPD expression using 151 resected non-small-cell lung cancer (NSCLC) patients postoperatively treated with a combination of tegafur and uracil (UFT). Eighty-two carcinomas were TS-positive, 105 carcinomas were OPRT-positive, 68 carcinomas were DPD-positive. No correlation was observed in the HSCORE between the TS and OPRT expression (r=0.203), between the TS and DPD expression (r=0.098), or between the OPRT and DPD expression (r=0.074). Regarding the survival of NSCLC patients treated with UFT, the 5-year survival rate of patients with TS-negative tumours was significantly higher than that with TS-positive tumours (P=0.0133). The 5-year survival rate of patients with OPRT-positive stage II to III tumours was significantly higher than that with OPRT-negative stage II to III tumours (P=0.0145). In addition, the 5-year survival rate of patients with DPD-negative tumours was also significantly higher than that with DPD-positive tumours (P=0.0004). A Cox multivariate regression analysis revealed the TS status (hazard ratio 2.663; P=0.0003), OPRT status (hazard ratio 2.543; P=0.0005), and DPD status (hazard ratio 2.840; P<0.0001) to all be significant prognostic factors for the survival of resected NSCLC patients postoperatively treated with UFT.