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    Prognostic significance of thymidylate synthase, dihydropyrimidine dehydrogenase and thymidine phosphorylase protein expression in colorectal cancer patients treated with or without 5-fluorouracil-based chemotherapy

    Access Status
    Open access via publisher
    Authors
    Soong, R.
    Shah, N.
    Salto-Tellez, M.
    Tai, B.
    Soo, R.
    Han, H.
    Ng, S.
    Tan, W.
    Zeps, Nikolajs
    Joseph, D.
    Diasio, R.
    Iacopetta, B.
    Date
    2008
    Type
    Journal Article
    
    Metadata
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    Citation
    Soong, R. and Shah, N. and Salto-Tellez, M. and Tai, B. and Soo, R. and Han, H. and Ng, S. et al. 2008. Prognostic significance of thymidylate synthase, dihydropyrimidine dehydrogenase and thymidine phosphorylase protein expression in colorectal cancer patients treated with or without 5-fluorouracil-based chemotherapy. Annals of Oncology. 19 (5): pp. 915-919.
    Source Title
    Annals of Oncology
    DOI
    10.1093/annonc/mdm599
    ISSN
    0923-7534
    URI
    http://hdl.handle.net/20.500.11937/38030
    Collection
    • Curtin Research Publications
    Abstract

    Background: Low tumour expression levels of thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD) and thymidine phosphorylase (TP) have been linked with improved outcome for colorectal cancer (CRC) patients treated with 5-fluorouracil (5-FU). It is unclear whether this occurs because such tumours have better prognosis or they are more sensitive to 5-FU treatment. Patients and methods: Associations between TS, DPD and TP levels, determined by tissue microarrays and immunohistochemistry, and survival was evaluated in 945 CRC patients according to treatment status. Results: Low TS and DPD expression associated with worse prognosis in stage II [hazard ratio (HR) = 1.69, 95% confidence interval (CI) (1.09-2.63) and HR = 1.92 (95% CI 1.23-2.94), respectively] and stage III CRC patients treated by surgery alone [HR = 1.39 (95% CI 0.92-2.13) and HR = 1.49 (95% CI 1.02-2.17), respectively]. Low TS, DPD and TP associated with trends for better outcome in stage III patients treated with 5-FU [HR = 0.81 (95% CI 0.49-1.33), HR = 0.70 (95% CI 0.42-1.15) and HR = 0.66 (95% CI 0.39-1.12), respectively]. Conclusion: Low TS and DPD expression are prognostic for worse outcome in CRC patients treated by surgery alone, whereas low TS, DPD and TP expression are prognostic for better outcome in patients treated with 5-FU chemotherapy. These results provide indirect evidence that low TS, DPD and TP protein expression are predictive of good response to 5-FU chemotherapy. © The Author 2008. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.

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