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Japanese Journal of Clinical Oncology Advance Access published online on November 17, 2008
Japanese Journal of Clinical Oncology, doi:10.1093/jjco/hyn121
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© The Author (2008). Published by Oxford University Press. All rights reserved

Comparison of 5-Fluorouracil-related Gene Expression Levels Between Adenocarcinomas and Squamous Cell Carcinomas of the Lung

Hiromi Ishihama1, Masayuki Chida1, Osamu Araki1, Yoko Karube1, Norio Seki1, Motohiko Tamura1, Hideo Umezu1, Koichi Honma2, Nobuhide Masawa2 and Shinichiro Miyoshi1

1 Department of Cardiothoracic Surgery
2 Department of Anatomic and Diagnostic Pathology, Dokkyo Medical University, Shimotsuga, Tochigi, Japan

For reprints and all correspondence: Shinichiro Miyoshi, Dokkyo Medical University, 880 Kitakobayashi, Mibu-machi, Shimotsuga, Tochigi 321-0293, Japan. E-mail: miyoshi{at}dokkyomed.ac.jp

Received August 12, 2008; accepted October 1, 2008

Background: A recent meta-analysis study showed that post-operative adjuvant chemotherapy with UFT, an oral combination drug composed of tegafur [prodrug of 5-fluorouracil (5-FU)] and uracil [inhibitor of dihydropyrimidine dehydrogenase (DPD)] was associated with improved survival in patients with lung adenocarcinomas, but not in those with lung squamous cell carcinomas.

Methods: We investigated the 5-FU-related gene expression levels of thymidylate synthase (TS), DPD, thymidine phosphorylase (TP) and orotate phosphoribosyl transferase (OPRT) in resected tumor specimens from 51 patients with adenocarcinomas and 47 with squamous cell carcinomas using quantitative reverse transcription–PCR, and compared those levels between the two histological types.

Results: The relative gene expression values of TS, TP and OPRT were significantly lower in adenocarcinomas compared with squamous cell carcinomas, 1.60 ± 0.86 versus 4.33 ± 3.40 (P < 0.001), 0.84 ± 0.52 versus 2.27 ± 1.16 (P = 0.006) and 9.59 ± 6.30 versus 16.94 ± 12.04 (P < 0.001), respectively. The relative gene expression value of DPD was significantly greater in adenocarcinomas than those in squamous cell carcinomas, 2.33 ± 1.22 versus 1.50 ± 1.20 (P = 0.01). Lower expressions of TS and TP were observed more in adenocarcinomas (89.8%) than in squamous cell carcinomas (48.9%) (P < 0.001).

Conclusion: These data may explain that post-operative adjuvant chemotherapy with UFT was associated with improved survival in stage I patients with adenocarcinoma, but less with squamous cell carcinoma.

Key Words: lung cancer • gene expression • UFT • thymidylate synthase • orotate phosphoribosyl transferase


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