title: Association of time to recurrence with thymidylate synthase and dihydropyrimidine dehydrogenase mRNA expression in stage II and III colorectal cancer.
abstract: Patients with International Union Against Cancer (UICC) stage IIb and III colon cancer and stage II and III rectal cancer may receive adjuvant chemotherapy with 5-fluorouracil (5-FU). High levels of thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) have been associated with resistance to 5-FU in advanced colorectal cancer. The aim of this study was to investigate the association of TS and DPD mRNA levels with recurrence-free survival in patients with colorectal cancer who are receiving adjuvant 5-FU-based chemotherapy. TS and DPD mRNA quantitation was retrospectively performed in primary colorectal cancer specimens from patients receiving adjuvant 5-FU using a reverse transcription- polymerase chain reaction technique. The median TS mRNA level in patients with a recurrence (n = 142) was 0.68, and in patients without a recurrence (n = 206) the median level was 0.80 (P < 0.01). Patients with a recurrence who had a low TS level (TS < or = 0.9; n = 102) had a median recurrence-free survival of 18 months (range 3.0 to 54 months), and those with a high TS level (TS > 0.9; n = 40) had a median recurrence-free survival of 11 months (range 1.7 to 53 months; P = 0.0024). There was no difference in the median recurrence-free survival of patients with low and high DPD mRNA levels. The TS mRNA level may be a useful marker to predict the time to recurrence in patients with colorectal cancer who are receiving adjuvant 5-FU treatment.
authors.affiliation: Department of General Surgery, University of Ulm, Ulm, Germany.
authors.forename: Marko
authors.initials: M
authors.lastname: Kornmann
authors.forename: Karl H
authors.initials: KH
authors.lastname: Link
authors.forename: Inga
authors.initials: I
authors.lastname: Galuba
authors.forename: Kati
authors.initials: K
authors.lastname: Ott
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Schwabe
authors.forename: Peter
authors.initials: P
authors.lastname: Häusler
authors.forename: Peter
authors.initials: P
authors.lastname: Scholz
authors.forename: Jörn
authors.initials: J
authors.lastname: Sträter
authors.forename: Sucan
authors.initials: S
authors.lastname: Polat
authors.forename: Bernhard
authors.initials: B
authors.lastname: Leibl
authors.forename: Erika
authors.initials: E
authors.lastname: Kettner
authors.forename: Christoph
authors.initials: C
authors.lastname: Schlichting
authors.forename: Wolfram
authors.initials: W
authors.lastname: Baumann
authors.forename: Harald
authors.initials: H
authors.lastname: Schramm
authors.forename: Ute
authors.initials: U
authors.lastname: Hecker
authors.forename: Karsten
authors.initials: K
authors.lastname: Ridwelski
authors.forename: Jürgen H
authors.initials: JH
authors.lastname: Vogt
authors.forename: Klaus-Ullrich
authors.initials: KU
authors.lastname: Zerbian
authors.forename: Frank
authors.initials: F
authors.lastname: Schütze
authors.forename: Ernst D
authors.initials: ED
authors.lastname: Kreuser
authors.forename: Detlev
authors.initials: D
authors.lastname: Behnke
authors.forename: Hans G
authors.initials: HG
authors.lastname: Beger
mesh_terms: D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use; D017024:Chemotherapy, Adjuvant; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000401:mortality* / Q000473:pathology; D042943:Dihydrouracil Dehydrogenase (NADP); D018572:Disease-Free Survival; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000201:enzymology* / Q000401:mortality; D010088:Oxidoreductases / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D012004:Rectal Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000401:mortality* / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013940:Thymidylate Synthase / Q000378:metabolism*
chemical_list: D000964:Antimetabolites, Antineoplastic; D012333:RNA, Messenger; D010088:Oxidoreductases; D042943:Dihydrouracil Dehydrogenase (NADP); D013940:Thymidylate Synthase; D005472:Fluorouracil