title: Thymidylate synthase messenger RNA expression in plasma from patients with colon cancer: prognostic potential.
abstract: OBJECTIVE
  Thymidylate synthase (TS), a critical target in fluorouracil-based chemotherapy, is a prognostic marker in colon carcinomas and a predictor of response to treatment. Tumor RNA has been detected in plasma from cancer patients and is associated with poor prognosis. This is the first study to examine extracellular TS mRNA in plasma from patients with colon carcinoma, and its possible relation with TS promoter enhancer region (TSER) polymorphism.
  
  
  METHODS
  TS expression was measured in plasma from 88 patients and 26 controls, and in a tumor subgroup of this series by quantitative PCR. Genotyping for TSER polymorphism was done in 60 patients. Clinicopathologic variables were correlated with these molecular changes.
  
  
  RESULTS
  TS mRNA was detected in plasma in 47% of patients, showing significant differences from healthy controls. Patients with TS mRNA in plasma had higher levels of TS in tumor tissue than patients without. The presence of TS mRNA was associated with lymph node metastases and more advanced stages. Polymorphism TSER 3/3 was found in 38% of cases, and was significantly correlated with high amounts of TS mRNA in plasma.
  
  
  CONCLUSIONS
  Our results suggest that TS mRNA in plasma originated from tumors, it may indicate poor prognosis and might help to classify tumors in Dukes' stages B and C. The TSER genotype may influence TS mRNA expression in plasma.
authors.affiliation: Deparment of Medical Oncology and Surgery, Hospital Universitario Puerta de Hierro, Madrid, Spain.
authors.forename: Vanesa
authors.initials: V
authors.lastname: Garcia
authors.forename: José M
authors.initials: JM
authors.lastname: García
authors.forename: Cristina
authors.initials: C
authors.lastname: Peña
authors.forename: Javier
authors.initials: J
authors.lastname: Silva
authors.forename: Gemma
authors.initials: G
authors.lastname: Domínguez
authors.forename: Alicia
authors.initials: A
authors.lastname: Hurtado
authors.forename: Isabel
authors.initials: I
authors.lastname: Alonso
authors.forename: Rufo
authors.initials: R
authors.lastname: Rodriguez
authors.forename: Mariano
authors.initials: M
authors.lastname: Provencio
authors.forename: Félix
authors.initials: F
authors.lastname: Bonilla
mesh_terms: D003110:Colonic Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012333:RNA, Messenger / Q000096:biosynthesis / Q000097:blood / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013940:Thymidylate Synthase / Q000097:blood / Q000235:genetics*
chemical_list: D012333:RNA, Messenger; D013940:Thymidylate Synthase