title: Thymidylate synthase expression in normal colonic mucosa: a predictive marker of toxicity in colorectal cancer patients receiving 5-fluorouracil-based adjuvant chemotherapy.
abstract: OBJECTIVE
  We retrospectively evaluated the relevance of thymidylate synthase (TS) expression in normal colonic mucosa as a predictive factor of toxicity in colorectal cancer patients receiving adjuvant fluorouracil (5-FU)-based chemotherapy.
  
  
  METHODS
  TS expression was immunohistochemically assessed on normal colonic mucosa from 50 patients with colorectal cancer Dukes' stages B (15 patients) and C (35 patients) treated with 5-FU-based adjuvant chemotherapy.
  
  
  RESULTS
  The incidence of grade 2-3 diarrhea and stomatitis (according to WHO) was demonstrated to be significantly higher in patients with low nuclear TS expression in normal mucosa than in those with high TS expression (p < 0.0001). Moreover, patients with low TS expression in normal colonic mucosa developed weight loss and worsening of the performance status (according to ECOG score) more commonly than patients with high TS expression (p = 0.005 and p = 0.02, respectively). Furthermore, low TS expression in normal colonic mucosa significantly correlated with a higher rate of a delay of chemotherapy courses, dose reduction and treatment discontinuation.
  
  
  CONCLUSIONS
  Immunohistochemical TS expression in normal colonic mucosa may represent an important predictive parameter for identifying a subset of patients with a high risk of developing severe 5-FU-related toxicities.
authors.affiliation: Medical Oncology Unit, University Campus Bio-Medico, Rome, Italy.
authors.forename: Daniele
authors.initials: D
authors.lastname: Santini
authors.forename: Bruno
authors.initials: B
authors.lastname: Vincenzi
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Perrone
authors.forename: Carla
authors.initials: C
authors.lastname: Rabitti
authors.forename: Domenico
authors.initials: D
authors.lastname: Borzomati
authors.forename: Marco
authors.initials: M
authors.lastname: Caricato
authors.forename: Annalisa
authors.initials: A
authors.lastname: La Cesa
authors.forename: Claudia
authors.initials: C
authors.lastname: Grilli
authors.forename: Alfio
authors.initials: A
authors.lastname: Verzì
authors.forename: Roberto
authors.initials: R
authors.lastname: Coppola
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Tonini
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects*; D014408:Biomarkers, Tumor / Q000032:analysis*; D017024:Chemotherapy, Adjuvant / Q000009:adverse effects; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000201:enzymology* / Q000473:pathology; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D012189:Retrospective Studies; D013940:Thymidylate Synthase / Q000032:analysis*; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; D013940:Thymidylate Synthase; D005472:Fluorouracil