title: The role of thymidylate synthase expression in prognosis and outcome of adjuvant chemotherapy in patients with rectal cancer.
abstract: OBJECTIVE
  We assessed the prognostic importance of the level of thymidylate synthase (TS) expression in patients with primary rectal cancer and whether, for Dukes' B and C cancer patients, the benefit of chemotherapy was associated with TS expression.
  
  
  METHODS
  The level of TS expression in the primary rectal cancers of 294 of 801 patients enrolled on protocol R-01 of the National Surgical Adjuvant Breast and Bowel Project (NSABP) was immunohistochemically assessed with the monoclonal antibody TS 106.
  
  
  RESULTS
  Forty-nine percent of patients whose tumors had low TS levels (n = 91) were disease free at 5 years compared with 27% of patients with high levels of TS (n = 203; P < .01). Moreover, 60% of patients with low TS levels were alive after 5 years compared with 40% of patients with high TS levels (P < .01). The level of TS protein was significantly associated with Dukes' stage (P < .01); patients with a more advanced Dukes' stage had a significantly higher level of TS. The level of TS expression remained prognostic for both disease-free survival (P < .01) and survival (P < .05) independent of Dukes' stage and other pathologic characteristics evaluated. Thirty-eight percent and 54% of patients with high TS levels (n = 71) were disease free and alive, respectively, after 5 years when treated with chemotherapy, compared with 17% and 31%, respectively, of similar patients when treated with surgery alone (n = 64) (P < .01). No difference was noted in disease-free survival (P = .46) or survival (P = .43) in patients with low TS levels.
  
  
  CONCLUSIONS
  The expression of TS is an important independent prognosticator of disease-free survival and survival in patients with rectal cancer. Adjuvant fluorouracil (5-FU)-based chemotherapy demonstrated significant improvement in disease-free and overall survival for patients with high TS levels. Prospective studies measuring TS levels will be needed to understand further the role of TS as a prognosticator of survival and chemotherapeutic benefit.
authors.affiliation: National Cancer Institute-Navy Medical Oncology Branch, National Cancer Institute, Bethesda, MD 20889.
authors.forename: P G
authors.initials: PG
authors.lastname: Johnston
authors.forename: E R
authors.initials: ER
authors.lastname: Fisher
authors.forename: H E
authors.initials: HE
authors.lastname: Rockette
authors.forename: B
authors.initials: B
authors.lastname: Fisher
authors.forename: N
authors.initials: N
authors.lastname: Wolmark
authors.forename: J C
authors.initials: JC
authors.lastname: Drake
authors.forename: B A
authors.initials: BA
authors.lastname: Chabner
authors.forename: C J
authors.initials: CJ
authors.lastname: Allegra
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant; D018572:Disease-Free Survival; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D009367:Neoplasm Staging; D011379:Prognosis; D011446:Prospective Studies; D012004:Rectal Neoplasms / Q000188:drug therapy* / Q000201:enzymology* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D012673:Semustine / Q000008:administration & dosage; D016019:Survival Analysis; D013940:Thymidylate Synthase / Q000378:metabolism*; D016896:Treatment Outcome; D014750:Vincristine / Q000008:administration & dosage
chemical_list: D012673:Semustine; D014750:Vincristine; D013940:Thymidylate Synthase; D005472:Fluorouracil