title: Thymidylate synthase expression pattern, expression level and single nucleotide polymorphism are predictors for disease-free survival in patients of colorectal cancer treated with 5-fluorouracil.
abstract: Several variables associated to thymidylate synthase (TS), the biological target of 5-fluorouracil (5FU) have been studied for their possible role as predictors of the clinical outcome and response to chemotherapy in colorectal cancer (CRC) patients. The level of protein expression and the number of variable tandem-repeats of a 28-bp sequence within the gene promoter have been proposed as predictive and/or prognostic factors with variable agreement, while consensus seems to be achieved with respect to the value of a single nucleotide polymorphism (SNP) described within this same region. More recently, an association between TS expression pattern and survival has been disclosed. Paraffin-embedded sections from 140 CRC patients were analyzed by immuno-histochemistry (Mab TS106) for TS levels and expression pattern. Also, VNTR and SNP were determined by polymerase-chain reaction (PCR) and restriction-length-fragment polymorphism (RFLP) in 123 and 112 patients, respectively. Cytoplasmic expression pattern tended to be associated to C SNP (p=0.06). Low TS expression levels, cytoplasmic expression pattern and C SNP arose as variables associated to longer progression-free survival (PFS) in patients treated with 5FU. Accordingly, patients having at least two favourable or unfavourable variables were classified respectively as 'low risk' and 'high risk', the former showing significantly longer PFS (p=0.0299). The possibility for designing a selection method for subsequent therapies is suggested on the basis of a probable combined effect of the above mentioned parameters but further studies in larger populations are needed to confirm these results.
authors.affiliation: Department of Pathology, Hospital Universitario de la Princesa, 28006 Madrid, Spain.
authors.forename: María-Encarnación
authors.initials: ME
authors.lastname: Fernández-Contreras
authors.forename: Sandra
authors.initials: S
authors.lastname: Sánchez-Prudencio
authors.forename: José-Javier
authors.initials: JJ
authors.lastname: Sánchez-Hernández
authors.forename: María-Luisa
authors.initials: ML
authors.lastname: García de Paredes
authors.forename: Javier P
authors.initials: JP
authors.lastname: Gisbert
authors.forename: Pedro
authors.initials: P
authors.lastname: Roda-Navarro
authors.forename: Carlos
authors.initials: C
authors.lastname: Gamallo
mesh_terms: D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000401:mortality / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D018598:Minisatellite Repeats; D009367:Neoplasm Staging; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D016019:Survival Analysis; D013940:Thymidylate Synthase / Q000037:antagonists & inhibitors / Q000235:genetics*; D013997:Time Factors
chemical_list: D000964:Antimetabolites, Antineoplastic; D013940:Thymidylate Synthase; D005472:Fluorouracil