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Thymidilate synthase expression predicts longer survival in patients with stage II colon cancer treated with 5-flurouracil independently of microsatellite instability

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Abstract

Background

5-Fluorouracil (5-FU) is the most commonly used therapeutic agent for colon cancer treatment. Several studies have evaluated in patients with colon cancer, either the role of genes involved in the 5-FU pathway, such as thymidylate synthase (TS), thymidine phosphorylase (TP) and dihydropyrimidine dehydrogenase (DPD) or the role of microsatellite instability (MSI) as prognostic or predictive markers for adjuvant chemotherapy efficacy, with discordant results. In this study we investigated the combined effect of TS, TP, DPD mRNA expression and MSI status in primary tumors of patients with colon cancer, all treated with 5-FU adjuvant therapy.

Methods

TS, TP and DPD expression levels were investigated by real-time quantitative RT-PCR on RNA extracts from formalin-fixed and paraffin-embedded tissues of 55 patients with colon adenocarcinoma. In the same case study MSI status was assessed on DNA extracts.

Results

A higher TS expression was significantly associated with a longer survival for patients with cancers of stage II (P < 0.01), but not for those with stage III (P = 0.68). In addition, in multivariate analysis, a higher TS expression was significantly associated with a decreased risk of death (HR 0.13, 95% CI 0.03–0.59, P < 0.01), while the MSI status did not have effects on patients’ survival.

Conclusions

This retrospective investigation suggests that TS gene expression at mRNA level can be a useful marker of better survival in patients (especially of those with cancers of stage II) receiving 5-FU adjuvant chemotherapy, independently of the MSI status.

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Acknowledgments

We would like to thank IMPACTS group for technical discussion in using archive tissues (ref. group involved in the European Project No 37211). This work was supported by grants from MIUR-Prin 2006 (project number 2006063220_003) and FIRB-MIUR. The authors also thank Dr. Valentina Melita for the English revision of the manuscript.

Conflict of interest statement

There are no conflicts of interest to declare.

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Authors and Affiliations

  1. ACADEM Department, Cattinara Hospital, University of Trieste, Surgical Pathology Bldg, Strada di Fiume 447, 34149, Trieste, Italy

    Marisa Donada, Serena Bonin, Ermanno Nardon, Alessandro De Pellegrin & Giorgio Stanta

  2. International Centre for Genetic Engineering and Biotechnology, Padriciano, 34149, Trieste, Italy

    Serena Bonin, Ermanno Nardon & Giorgio Stanta

  3. Department of Biomedical Sciences, University of Trieste, via Giorgieri 7, 34149, Trieste, Italy

    Giuliana Decorti

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  1. Marisa Donada
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  2. Serena Bonin
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  4. Alessandro De Pellegrin
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  5. Giuliana Decorti
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  6. Giorgio Stanta
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Correspondence to Giorgio Stanta.

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Donada, M., Bonin, S., Nardon, E. et al. Thymidilate synthase expression predicts longer survival in patients with stage II colon cancer treated with 5-flurouracil independently of microsatellite instability. J Cancer Res Clin Oncol 137, 201–210 (2011). https://doi.org/10.1007/s00432-010-0872-1

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  • DOI: https://doi.org/10.1007/s00432-010-0872-1

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