Elsevier

Annals of Oncology

Volume 16, Issue 10, October 2005, Pages 1646-1653
Annals of Oncology

Original article
Gastrointestinal tumors
Predictive value of thymidylate synthase and dihydropyrimidine dehydrogenase protein expression on survival in adjuvantly treated stage III colon cancer patients

https://doi.org/10.1093/annonc/mdi316Get rights and content
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Abstract

Background: The predictive value of thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) expression on long-term survival by influencing 5-fluorouracil (5-FU) effect were determined in primary tumours and node metastases of stage III colon cancer patients treated adjuvantly with 5-FU regimens (n = 391). The effect of TP53 mutation status, which is thought to be functionally linked to TS inhibition, was also examined.

Patients and methods: TS and DPD protein expression was determined by immunohistochemical analysis using tissue microarrays of these colon tumours. Two hundred and twenty tumours had already been screened in a previous study for TP53 mutations.

Results: Low TS protein levels in primary stage III colon tumours appeared to be associated with mucinous histology and low DPD protein levels with young age at time of randomisation. Concordance between TS and DPD expression in primary and metastatic tumours was low. No associations were found between disease-free survival (DFS) and TS or DPD protein levels. When stratified by TP53 mutation status DFS did not differ with TS expression.

Conclusions: Expression of TS and DPD proteins is not predictive for survival in patients with stage III colon cancer treated adjuvantly with 5-FU regimens. TS protein levels did not alter the effect of TP53 mutation status.

Keywords

colon cancer
dihydropyrimidine dehydrogenase
prediction 5-fluorouracil regimen
thymidylate synthase
TP53

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