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Annals of Oncology Advance Access originally published online on July 12, 2005
Annals of Oncology 2005 16(10):1646-1653; doi:10.1093/annonc/mdi316
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© 2005 European Society for Medical Oncology

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

J. L. Westra1, H. Hollema2, M. Schaapveld3, I. Platteel2, K. A. Oien4, W. N. Keith4, R. Mauritz5, G. J. Peters5, C. H. C. M. Buys1, R. M. W. Hofstra1 and J. Th. M. Plukker6,*

Departments of 1 Medical Genetics, 2 Pathology and 6 Surgery, University Medical Center Groningen, Groningen; 3 Comprehensive Cancer Centre North Netherlands, Groningen, The Netherlands; 4 Department of Medical Oncology, University of Glasgow, Cancer Research UK Beatson Laboratories, Glasgow, UK; 5 Department of Medical Oncology, Free University Hospital, Amsterdam, The Netherlands

* Correspondence to: Dr J. Plukker, Department of Surgery, UMCG, Hanzeplein 1, 9700RB, Groningen, The Netherlands. Tel: +31-50-3612317; Fax: +31-50-3614873; E-mail: j.th.plukker{at}chir.umcg.nl

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.

Key words: colon cancer, dihydropyrimidine dehydrogenase, prediction 5-fluorouracil regimen, thymidylate synthase, TP53


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