1. PML as a potential predictive factor of oxaliplatin/fluoropyrimidine-based first line chemotherapy efficacy in colorectal cancer patients.
- Author
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Vincenzi B, Santini D, Perrone G, Graziano F, Loupakis F, Schiavon G, Frezza AM, Ruzzo AM, Rizzo S, Crucitti P, Galluzzo S, Zoccoli A, Rabitti C, Muda AO, Russo A, Falcone A, and Tonini G
- Subjects
- Adult, Aged, Antimetabolites, Antineoplastic therapeutic use, Capecitabine, Colorectal Neoplasms secondary, Deoxycytidine analogs & derivatives, Deoxycytidine therapeutic use, Drug Resistance, Neoplasm physiology, Female, Fluorouracil analogs & derivatives, Humans, Leucovorin therapeutic use, Male, Middle Aged, Organoplatinum Compounds therapeutic use, Oxaliplatin, Oxaloacetates, Predictive Value of Tests, Promyelocytic Leukemia Protein, Retrospective Studies, Survival Rate, Antineoplastic Agents therapeutic use, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Colorectal Neoplasms drug therapy, Colorectal Neoplasms metabolism, Fluorouracil therapeutic use, Nuclear Proteins metabolism, Transcription Factors metabolism, Tumor Suppressor Proteins metabolism
- 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., (Copyright © 2011 Wiley Periodicals, Inc.)
- Published
- 2012
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