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. 2006 Apr;21(3):238-47. doi: 10.1007/s00384-005-0767-9. Epub 2005 Aug 13.


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.

MeSH terms

  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Colonic Neoplasms / enzymology
  • Colonic Neoplasms / genetics
  • Colorectal Neoplasms / drug therapy
  • Colorectal Neoplasms / enzymology
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / pathology*
  • Colorectal Neoplasms / surgery
  • Combined Modality Therapy
  • Dihydrouracil Dehydrogenase (NADP) / genetics*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Predictive Value of Tests
  • Prognosis
  • RNA, Messenger / genetics*
  • Rectal Neoplasms / enzymology
  • Rectal Neoplasms / genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • Thymidine Phosphorylase / genetics*
  • Thymidylate Synthase / genetics*


  • RNA, Messenger
  • Dihydrouracil Dehydrogenase (NADP)
  • Thymidylate Synthase
  • Thymidine Phosphorylase