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Thymidine phosphorylase, dihydropyrimidine dehydrogenase and thymidylate synthase mRNA expression in primary colorectal tumors—correlation to tumor histopathology and clinical follow-up

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International Journal of Colorectal Disease Aims and scope Submit manuscript

Abstract

Aim

Evaluation of thymidine phosphorylase (TP), dihydropyrimidine dehydrogenase (DPD), and thymidylate synthase (TS) mRNA levels in formalin-fixed, and paraffin-embedded tissues of patients with colorectal cancer and their prognostic and/or predictive value.

Materials and methods

Total RNA was isolated from microdissected, formalin-fixed, and paraffin-embedded tissues (controls and tumor) and subjected to quantitative RT-PCR (QRT-PCR) in the LightCycler system. Resulting mRNA levels correlated to tumor histology (n=102) and the clinical follow-up in patients treated by resection alone (n=40) and by resection plus adjuvant 5-FU-based chemotherapy (n=52).

Results

Correlation to histopathological parameters revealed a significant association between tumor stage and the TP mRNA level (T and N category and UICC) as well as the TP:DPD (T and N category and UICC) and TS:DPD (T category) ratio. In addition, tumor differentiation was correlated to the TS mRNA level and the TS:DPD ratio. Finally, the TS:DPD ratio was a prognostic marker for overall survival in patients receiving resection alone (p=0.032). Moreover, a high TP:DPD ratio (>8.1; p=0.002) and, marginally, low DPD (<8.2; p=0.05) mRNA levels significantly correlated to disease-free survival.

Conclusion

We present a novel, standardized approach for TP, DPD, and TS mRNA quantification in archival tissue specimens and applied this to a large series of primary colorectal tumors. Correlations to histopathological parameters and clinical follow-up revealed an association of TP, DPD and TS mRNA expression patterns with tumor stage and suggested new prognostic and predictive markers for patients with colorectal cancer.

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Acknowledgements

We thank Mrs. Diana Grewe for expert technical assistance.

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Authors and Affiliations

  1. Pathologisches Institut, Universitätsklinikum Freiburg, Albertstrasse 19, 79104, Freiburg, Germany

    Silke Lassmann & Martin Werner

  2. Institut für Medizinische Statistik und Epidemiologie, Klinikum rechts der Isar, Munich, Germany

    Michael Hennig

  3. Chirurgische Klinik, Klinikum rechts der Isar, Munich, Germany

    Robert Rosenberg & Hjalmar Nekarda

  4. Institut für Pathologie, Klinikum rechts der Isar, Munich, Germany

    Jörg Nährig, Joachim Schreglmann & Heinz Höfler

  5. Roche Diagnostics GmbH, Penzberg, Germany

    Friedemann Krause & Manuela Poignee-Heger

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  1. Silke Lassmann
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Correspondence to Silke Lassmann.

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Lassmann, S., Hennig, M., Rosenberg, R. et al. Thymidine phosphorylase, dihydropyrimidine dehydrogenase and thymidylate synthase mRNA expression in primary colorectal tumors—correlation to tumor histopathology and clinical follow-up. Int J Colorectal Dis 21, 238–247 (2006). https://doi.org/10.1007/s00384-005-0767-9

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  • DOI: https://doi.org/10.1007/s00384-005-0767-9

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