6533b7d0fe1ef96bd125b954

RESEARCH PRODUCT

PML as a potential predictive factor of oxaliplatin/fluoropyrimidine-based first line chemotherapy efficacy in colorectal cancer patients

Fotios LoupakisAlfredo FalconeSergio RizzoGaia SchiavonCarla RabittiPierfilippo CrucittiDaniele SantiniAnnamaria RuzzoGiuseppe ToniniGiuseppe PerroneBruno VincenziAnna Maria FrezzaFrancesco GrazianoAntonio RussoAndrea Onetti MudaAlice ZoccoliSara Galluzzo

subject

OncologyMaleOrganoplatinum CompoundsOxaloacetatesPhysiologyColorectal cancerSettore MED/06 - Oncologia MedicavirusesClinical BiochemistryCellLeucovorinPromyelocytic Leukemia Proteinmedicine.disease_causeDeoxycytidineAntineoplastic Combined Chemotherapy Protocolsbiologyvirus diseasesNuclear ProteinsMiddle AgedOxaliplatinSurvival Ratemedicine.anatomical_structureImmunohistochemistryoxaliplatin/fluoropyrimidineFemaleFluorouracilColorectal Neoplasmsmedicine.drugAdultmedicine.medical_specialtyAntimetabolites AntineoplasticPML; oxaliplatin/fluoropyrimidine; colorectal cancerAntineoplastic Agentscolorectal cancerPromyelocytic leukemia proteinPredictive Value of TestsInternal medicinemedicineHumansCapecitabineAgedRetrospective StudiesPMLbusiness.industryTumor Suppressor ProteinsRetrospective cohort studyCell Biologymedicine.diseaseOxaliplatinApoptosisDrug Resistance Neoplasmbiology.proteinCarcinogenesisbusinessTranscription Factors

description

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. J. Cell. Physiol. 227: 927–933, 2012. © 2011 Wiley Periodicals, Inc.

10.1002/jcp.22801http://hdl.handle.net/10447/77113