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

R. Soong, N. Shah, M. Salto-Tellez, B. C. Tai, R. A. Soo, H. C. Han, S. S. Ng, W. L. Tan, N. Zeps, D. Joseph, Robert B Diasio, B. Iacopetta

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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.

Original languageEnglish (US)
Pages (from-to)915-919
Number of pages5
JournalAnnals of Oncology
Volume19
Issue number5
DOIs
StatePublished - May 2008
Externally publishedYes

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Dihydrouracil Dehydrogenase (NADP)
Thymidine Phosphorylase
Thymidylate Synthase
Fluorouracil
Colorectal Neoplasms
Confidence Intervals
Drug Therapy
Proteins
Neoplasms
Immunohistochemistry
Survival
Therapeutics

Keywords

  • Colorectal cancer
  • Fluorouracil
  • Predictive
  • Prognostic
  • Thymidylate synthase

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Prognostic significance of thymidylate synthase, dihydropyrimidine dehydrogenase and thymidine phosphorylase protein expression in colorectal cancer patients treated with or without 5-fluorouracil-based chemotherapy. / Soong, R.; Shah, N.; Salto-Tellez, M.; Tai, B. C.; Soo, R. A.; Han, H. C.; Ng, S. S.; Tan, W. L.; Zeps, N.; Joseph, D.; Diasio, Robert B; Iacopetta, B.

In: Annals of Oncology, Vol. 19, No. 5, 05.2008, p. 915-919.

Research output: Contribution to journalArticle

Soong, R. ; Shah, N. ; Salto-Tellez, M. ; Tai, B. C. ; Soo, R. A. ; Han, H. C. ; Ng, S. S. ; Tan, W. L. ; Zeps, N. ; Joseph, D. ; Diasio, Robert B ; Iacopetta, B. / Prognostic significance of thymidylate synthase, dihydropyrimidine dehydrogenase and thymidine phosphorylase protein expression in colorectal cancer patients treated with or without 5-fluorouracil-based chemotherapy. In: Annals of Oncology. 2008 ; Vol. 19, No. 5. pp. 915-919.
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title = "Prognostic significance of thymidylate synthase, dihydropyrimidine dehydrogenase and thymidine phosphorylase protein expression in colorectal cancer patients treated with or without 5-fluorouracil-based chemotherapy",
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.",
keywords = "Colorectal cancer, Fluorouracil, Predictive, Prognostic, Thymidylate synthase",
author = "R. Soong and N. Shah and M. Salto-Tellez and Tai, {B. C.} and Soo, {R. A.} and Han, {H. C.} and Ng, {S. S.} and Tan, {W. L.} and N. Zeps and D. Joseph and Diasio, {Robert B} and B. Iacopetta",
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T1 - Prognostic significance of thymidylate synthase, dihydropyrimidine dehydrogenase and thymidine phosphorylase protein expression in colorectal cancer patients treated with or without 5-fluorouracil-based chemotherapy

AU - Soong, R.

AU - Shah, N.

AU - Salto-Tellez, M.

AU - Tai, B. C.

AU - Soo, R. A.

AU - Han, H. C.

AU - Ng, S. S.

AU - Tan, W. L.

AU - Zeps, N.

AU - Joseph, D.

AU - Diasio, Robert B

AU - Iacopetta, B.

PY - 2008/5

Y1 - 2008/5

N2 - 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.

AB - 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.

KW - Colorectal cancer

KW - Fluorouracil

KW - Predictive

KW - Prognostic

KW - Thymidylate synthase

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