title: Topoisomerase-I, thymidylate synthase primary tumour expression and clinical efficacy of 5-FU/CPT-11 chemotherapy in advanced colorectal cancer patients.
abstract: While several studies have reported that thymidylate synthase (TS) tumour expression can be a reliable predictive marker of clinical response to 5-Fluorouracil (5-FU) for advanced colorectal cancer patients, only a few studies that searched for predictive factors of irinotecan (CPT-11) clinical response are available. The aim of the present study has been to verify the predictive value of immunohistochemical topoisomerase-I (Topo-I) and TS primary tumour expression in a consecutive series of 62 advanced colorectal cancer patients that received a first line 5-FU/CPT-11 chemotherapy. TS and Topo-I immunostaining was observed in 76% and 43% of tumours, respectively, resulting in a significant relationship within each tumour (r=0.365, p<0.004). Patients with different TS tumour expression showed a similar percentage of Objective Clinical Response, OR (40% vs. 28% of OR in low and high TS-expressing tumours, respectively, p=ns); also, patients with different Topo-I tumour expression did not show a different probability of OR (39% vs. 29% of OR in high and low Topo-I expressing tumours, respectively; p=ns). The tumour expression of these 2 biomarkers also did not impact on time to progression and overall survival of patients. Furthermore, the combined analysis of TS and Topo-I tumour status did not permit to individualize subgroups of patients with different probability of OR. With multivariate analysis, only patient Performance Status significantly impacted on OS (Hazard ratio 4.87; p=0.02) of these patients. We can conclude that high TS tumour expression seems not to preclude a clinical activity for 5-FU/CPT-11 polichemotherapy in advanced colorectal cancer patients; furthermore, clinical response and prognosis of colorectal cancer patients treated with 5-FU/CPT-11 regimen do not differ in tumours with different TS or Topo-I expression.
authors.affiliation: Clinical Experimental Oncology Laboratory, National Cancer Institute-Bari, Bari, Italy. paradiso.io.bari@virgilio.it
authors.forename: Angelo
authors.initials: A
authors.lastname: Paradiso
authors.forename: JanMing
authors.initials: J
authors.lastname: Xu
authors.forename: Anita
authors.initials: A
authors.lastname: Mangia
authors.forename: Annalisa
authors.initials: A
authors.lastname: Chiriatti
authors.forename: Gianni
authors.initials: G
authors.lastname: Simone
authors.forename: Alfredo
authors.initials: A
authors.lastname: Zito
authors.forename: Severino
authors.initials: S
authors.lastname: Montemurro
authors.forename: Francesco
authors.initials: F
authors.lastname: Giuliani
authors.forename: Evaristo
authors.initials: E
authors.lastname: Maiello
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Colucci
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D004264:DNA Topoisomerases, Type I / Q000096:biosynthesis*; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D020869:Gene Expression Profiling; D006801:Humans; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D000077146:Irinotecan; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D015999:Multivariate Analysis; D011379:Prognosis; D013940:Thymidylate Synthase / Q000096:biosynthesis*; D016896:Treatment Outcome
chemical_list: D000077146:Irinotecan; D013940:Thymidylate Synthase; D004264:DNA Topoisomerases, Type I; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin