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

Lassmann, S; Hennig, M; Rosenberg, R; Nährig, J; Schreglmann, J; Krause, F; Poignee-Heger, M; Nekarda, H; Höfler, H; Werner, M

doi:10.1007/s00384-005-0767-9

journal article

Title:: Thymidine phosphorylase, dihydropyrimidine dehydrogenase and thymidylate synthase mRNA expression in primary colorectal tumors-correlation to tumor histopathology and clinical follow-up.
Document type:: Journal Article; Article
Author(s):: Lassmann, S; Hennig, M; Rosenberg, R; Nährig, J; Schreglmann, J; Krause, F; Poignee-Heger, M; Nekarda, H; Höfler, H; Werner, M
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.
Journal title abbreviation:: Int J Colorectal Dis
Year:: 2006
Journal volume:: 21
Journal issue:: 3
Pages contribution:: 238-47
Language:: eng
Fulltext / DOI:: doi:10.1007/s00384-005-0767-9
Pubmed ID:: http://view.ncbi.nlm.nih.gov/pubmed/16132996
Print-ISSN:: 0179-1958
TUM Institution:: Chirurgische Klinik und Poliklinik; Institut für Allgemeine Pathologie und Pathologische Anatomie; Institut für Medizinische Statistik und Epidemiologie
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