title: Thymidine phosphorylase, dihydropyrimidine dehydrogenase and thymidylate synthase mRNA expression in primary colorectal tumors-correlation to tumor histopathology and clinical follow-up.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Pathologisches Institut, Universitätsklinikum Freiburg, Albertstrasse 19, 79104, Freiburg, Germany. silke.lassmann@uniklinik-freiburg.de
authors.forename: Silke
authors.initials: S
authors.lastname: Lassmann
authors.forename: Michael
authors.initials: M
authors.lastname: Hennig
authors.forename: Robert
authors.initials: R
authors.lastname: Rosenberg
authors.forename: Jörg
authors.initials: J
authors.lastname: Nährig
authors.forename: Joachim
authors.initials: J
authors.lastname: Schreglmann
authors.forename: Friedemann
authors.initials: F
authors.lastname: Krause
authors.forename: Manuela
authors.initials: M
authors.lastname: Poignee-Heger
authors.forename: Hjalmar
authors.initials: H
authors.lastname: Nekarda
authors.forename: Heinz
authors.initials: H
authors.lastname: Höfler
authors.forename: Martin
authors.initials: M
authors.lastname: Werner
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D003110:Colonic Neoplasms / Q000201:enzymology / Q000235:genetics; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics* / Q000473:pathology* / Q000601:surgery; D003131:Combined Modality Therapy; D042943:Dihydrouracil Dehydrogenase (NADP) / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics*; D012004:Rectal Neoplasms / Q000201:enzymology / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013939:Thymidine Phosphorylase / Q000235:genetics*; D013940:Thymidylate Synthase / Q000235:genetics*
chemical_list: D012333:RNA, Messenger; D042943:Dihydrouracil Dehydrogenase (NADP); D013940:Thymidylate Synthase; D013939:Thymidine Phosphorylase