title: PML as a potential predictive factor of oxaliplatin/fluoropyrimidine-based first line chemotherapy efficacy in colorectal cancer patients.
abstract: PML regulates a wide range of pathways involved in tumorigenesis, such as apoptosis, which is also one of the main mechanisms through which oxaliplatin and fluoropyrimidine exert their antineoplastic activity. The present study aims to investigate PML expression as a predictive factor of oxaliplatin/fluoropyrimidine therapy efficacy. Seventy-four metastatic colorectal cancer patients who received oxaliplatin/floropyrimidine-based first line therapy have been included in this retrospective study. PML expression was assessed by immunohistochemistry. PML down-regulation was detected in 39 (52.7%) patients (14 complete and 25 partial PML loss). RR was significantly lower (25.6%) in patients with PML down-regulation than in patients with preserved PML expression (60%) (P = 0.006). Median TTP was 5.5 months when PML was down-regulated versus 11.9 months in case of preserved PML expression (P < 0.0001). A statistical significant difference was also detected in OS (15.6 and 24.5 months, respectively, P = 0.003). The impact of PML down-regulation on TTP and OS was statistically significant also in a multivariate model. This study represents the first evidence of a possible correlation between PML protein expression and outcome of metastatic colorectal cancer patients treated with oxaliplatin/fluoropyrimidine-based first line therapy.
authors.affiliation: Department of Oncology, University Campus Bio-Medico, Rome, Italy.
authors.forename: Bruno
authors.initials: B
authors.lastname: Vincenzi
authors.forename: Daniele
authors.initials: D
authors.lastname: Santini
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Perrone
authors.forename: Francesco
authors.initials: F
authors.lastname: Graziano
authors.forename: Fotios
authors.initials: F
authors.lastname: Loupakis
authors.forename: Gaia
authors.initials: G
authors.lastname: Schiavon
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Frezza
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Ruzzo
authors.forename: Sergio
authors.initials: S
authors.lastname: Rizzo
authors.forename: Pierfilippo
authors.initials: P
authors.lastname: Crucitti
authors.forename: Sara
authors.initials: S
authors.lastname: Galluzzo
authors.forename: Alice
authors.initials: A
authors.lastname: Zoccoli
authors.forename: Carla
authors.initials: C
authors.lastname: Rabitti
authors.forename: Andrea Onetti
authors.initials: AO
authors.lastname: Muda
authors.forename: Antonio
authors.initials: A
authors.lastname: Russo
authors.forename: Alfredo
authors.initials: A
authors.lastname: Falcone
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Tonini
mesh_terms: D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000069287:Capecitabine; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000556:secondary; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000627:therapeutic use; D019008:Drug Resistance, Neoplasm / Q000502:physiology; D005260:Female; D005472:Fluorouracil / Q000031:analogs & derivatives / Q000627:therapeutic use*; D006801:Humans; D002955:Leucovorin / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000378:metabolism*; D009944:Organoplatinum Compounds / Q000627:therapeutic use; D000077150:Oxaliplatin; D010071:Oxaloacetates; D011237:Predictive Value of Tests; D000071156:Promyelocytic Leukemia Protein; D012189:Retrospective Studies; D015996:Survival Rate; D014157:Transcription Factors / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000378:metabolism*
chemical_list: D000964:Antimetabolites, Antineoplastic; D000970:Antineoplastic Agents; D009687:Nuclear Proteins; D009944:Organoplatinum Compounds; D010071:Oxaloacetates; D000071156:Promyelocytic Leukemia Protein; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D000077150:Oxaliplatin; D003841:Deoxycytidine; C070576:PML protein, human; D000069287:Capecitabine; D002955:Leucovorin; D005472:Fluorouracil