title: Correlation between thymidylate synthase protein expression and gene polymorphism with clinicopathological parameters in colorectal carcinoma.
abstract: 5-Fluorouracil (5-FU) represents the basis of chemotherapy for colorectal carcinoma, inhibiting thymidylate synthase (TS), an essential enzyme for DNA replication. Previous studies have associated high TS protein expression by tumor cells with poor outcome of patients with colorectal carcinoma, but others have refuted these findings. In view of the potential role of TS as predictive parameter and the lack of consensus in the literature, the present study compared 2 methods: protein expression and gene polymorphism, correlating them with clinicopathological findings. Immunohistochemical detection of TS in tumor cells and detection of gene polymorphism in the blood were performed in 32 patients with colorectal carcinoma treated with 5-FU. No correlation was found between TS protein expression and gene polymorphism. Neither method correlated with survival, tumor staging, and tumor histological grading. This result possibly reflects a complex tumor response to 5-FU therapy, where TS is just one of the involved proteins.
authors.affiliation: Laboratory of Investigative and Molecular Pathology, State University of Campinas Medical School, Campinas, São Paulo, Brazil.
authors.forename: Luciana R
authors.initials: LR
authors.lastname: Moreira
authors.forename: André Almeida
authors.initials: AA
authors.lastname: Schenka
authors.forename: Paulo
authors.initials: P
authors.lastname: Latuff Filho
authors.forename: Helvia
authors.initials: H
authors.lastname: Nascimento
authors.forename: Carmen Silvia
authors.initials: CS
authors.lastname: Passos Lima
authors.forename: Miriam Aparecida
authors.initials: MA
authors.lastname: Silva Trevisan
authors.forename: José
authors.initials: J
authors.lastname: Vassallo
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000032:analysis; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics*; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011379:Prognosis; D012189:Retrospective Studies; D016019:Survival Analysis; D013940:Thymidylate Synthase / Q000096:biosynthesis* / Q000235:genetics*
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D013940:Thymidylate Synthase; D005472:Fluorouracil