title: Topical 5-Fluorouracil is a Novel Targeted Therapy for the Keratocystic Odontogenic Tumor.
abstract: OBJECTIVE
  The antimetabolite drug, 5-fluorouracil (5-FU), is used in the treatment of various cancers, including basal cell carcinomas (BCCs). The authors hypothesized that keratocystic odontogenic tumors (KOTs) would respond to 5-FU treatment because of their similarities to BCCs in molecular etiopathogenesis.
  
  
  METHODS
  An ambispective cohort study of the treatment efficacy of topical 5-FU on KOTs was conducted. Independent variables included the topical application of 5% 5-FU or modified Carnoy's solution (MC) after enucleation and peripheral ostectomy at the University of Toronto from 2006 through 2014. Outcome variables included time to recurrence and peripheral nerve injury. KOT specimens in these patients were immunostained with p53, Ki-67, thymidylate synthetase (TS), thymidylate phosphorylase (TP), and dihydropyrimidine dehydrogenase (DPD) antibodies. Semiquantitative staining scores were calculated for all immunohistochemistry sections examined. Descriptive statistics were computed using Fisher exact test and Kaplan-Meier analysis as appropriate with the P value set at .05.
  
  
  RESULTS
  Thirty-two patients with 32 KOTs were reviewed (41% in women and 59% in men). There were no KOT recurrences in the 5-FU group (n = 11), whereas there were 4 recurrences in the MC group (n = 21; P = .190). There was a significantly lower incidence of inferior alveolar nerve paresthesia with 5-FU treatment (P = .039). Immunohistochemical staining showed upregulation of TP (P < .0001) and DPD (P < .0001) and no change in TS (P > .05) in inflamed KOTs.
  
  
  CONCLUSIONS
  5-FU effectively treats KOTs with less postoperative morbidity than conventional treatment with MC. Low TS and upregulated TP expressions in inflamed KOTs suggest increased 5-FU efficacy in inflamed KOTs. Topical 5-FU is a novel therapy for KOTs and provides a targeted molecular approach to treatment.
authors: Chief Resident, Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, University of Toronto, Toronto, ON, Canada.
authors: Nicholas J
authors: NJ
authors: Ledderhof
authors: Assistant Professor, Department of Oral and Maxillofacial Surgery, University of Toronto, Toronto, ON, Canada.
authors: Marco F
authors: MF
authors: Caminiti
authors: Professor and Head, Department of Oral Pathology and Oral Medicine, Faculty of Dentistry, University of Toronto, Toronto, ON, Canada.
authors: Grace
authors: G
authors: Bradley
authors: Assistant Professor and Head, Department of Oral and Maxillofacial Surgery, University of Toronto, Toronto, ON, Canada. Electronic address: david.lam@utoronto.ca.
authors: David K
authors: DK
authors: Lam
mesh_terms: D000287:Administration, Topical; D000328:Adult; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage*; D003131:Combined Modality Therapy; D042943:Dihydrouracil Dehydrogenase (NADP); D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage*; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D019394:Ki-67 Antigen; D008297:Male; D009807:Odontogenic Cysts / Q000473:pathology*; D009808:Odontogenic Tumors / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology* / Q000601:surgery; D013939:Thymidine Phosphorylase; D013940:Thymidylate Synthase; D016896:Treatment Outcome; D016159:Tumor Suppressor Protein p53
chemical_list: D000964:Antimetabolites, Antineoplastic; D019394:Ki-67 Antigen; D016159:Tumor Suppressor Protein p53; D042943:Dihydrouracil Dehydrogenase (NADP); D013940:Thymidylate Synthase; D013939:Thymidine Phosphorylase; D005472:Fluorouracil