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International Journal of Colorectal Disease
Published in: International Journal of Colorectal Disease 3/2006

01-04-2006 | Original Article

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

Authors: Silke Lassmann, Michael Hennig, Robert Rosenberg, Jörg Nährig, Joachim Schreglmann, Friedemann Krause, Manuela Poignee-Heger, Hjalmar Nekarda, Heinz Höfler, Martin Werner

Published in: International Journal of Colorectal Disease | Issue 3/2006

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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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Metadata
Title
Thymidine phosphorylase, dihydropyrimidine dehydrogenase and thymidylate synthase mRNA expression in primary colorectal tumors—correlation to tumor histopathology and clinical follow-up
Authors
Silke Lassmann
Michael Hennig
Robert Rosenberg
Jörg Nährig
Joachim Schreglmann
Friedemann Krause
Manuela Poignee-Heger
Hjalmar Nekarda
Heinz Höfler
Martin Werner
Publication date
01-04-2006
Publisher
Springer-Verlag
Published in
International Journal of Colorectal Disease / Issue 3/2006
Print ISSN: 0179-1958
Electronic ISSN: 1432-1262
DOI
https://doi.org/10.1007/s00384-005-0767-9

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