INTRODUCTION: Methylation of the promoter of the MGMT gene and MGMT protein expression are recognized as predictive markers for response to alkylating chemotherapy in glioblastoma (GB). MATERIAL AND METHODS: We have assessed MGMT methylation with the methylation-specific polymerase chain reaction (MSP) in tumor samples from 70 GB patients and in serum samples from 37 of these patients. We have also assessed MGMT protein expression by immunohistochemical (IHC) analysis in tissue samples from 63 of these patients. RESULTS: We found concordance between MGMT methylation status in tissue and serum (Cohen's Kappa = 0.586; p<0.0001). MSP for detection of non-methylated MGMT promoter in serum showed a sensitivity of 95.4% and a specificity of 60%, while the IHC methylation test showed a low specificity (8.9%). Patients whose MGMT promoter was methylated in tissue attained longer progression-free and overall survival. In the multivariate analysis, serum MGMT promoter methylation emerged as an independent factor for longer progression-free and overall survival. CONCLUSION: Serum-based MGMT methylation analysis offers a promising alternative to tumor-based MGMT analysis in cases where tissue samples are unavailable.
INTRODUCTION: Methylation of the promoter of the MGMT gene and MGMT protein expression are recognized as predictive markers for response to alkylating chemotherapy in glioblastoma (GB). MATERIAL AND METHODS: We have assessed MGMT methylation with the methylation-specific polymerase chain reaction (MSP) in tumor samples from 70 GB patients and in serum samples from 37 of these patients. We have also assessed MGMT protein expression by immunohistochemical (IHC) analysis in tissue samples from 63 of these patients. RESULTS: We found concordance between MGMT methylation status in tissue and serum (Cohen's Kappa = 0.586; p<0.0001). MSP for detection of non-methylated MGMT promoter in serum showed a sensitivity of 95.4% and a specificity of 60%, while the IHC methylation test showed a low specificity (8.9%). Patients whose MGMT promoter was methylated in tissue attained longer progression-free and overall survival. In the multivariate analysis, serum MGMT promoter methylation emerged as an independent factor for longer progression-free and overall survival. CONCLUSION: Serum-based MGMT methylation analysis offers a promising alternative to tumor-based MGMT analysis in cases where tissue samples are unavailable.
Authors: Carme Balaña; Jose Luis Ramirez; Miquel Taron; Yannis Roussos; Aurelio Ariza; Rosa Ballester; Carme Sarries; Pedro Mendez; Jose Javier Sanchez; Rafael Rosell Journal: Clin Cancer Res Date: 2003-04 Impact factor: 12.531
Authors: Marta Brell; Avelina Tortosa; Eugenia Verger; Juan Miguel Gil; Nuria Viñolas; Salvador Villá; Juan José Acebes; Lluis Caral; Teresa Pujol; Isidro Ferrer; Teresa Ribalta; Francesc Graus Journal: Clin Cancer Res Date: 2005-07-15 Impact factor: 12.531
Authors: C Balaña; J Capellades; P Teixidor; I Roussos; R Ballester; M Cuello; A Arellano; R Florensa; R Rosell Journal: Clin Transl Oncol Date: 2007-12 Impact factor: 3.405
Authors: Johan M Kros; Dana M Mustafa; Lennard J M Dekker; Peter A E Sillevis Smitt; Theo M Luider; Ping-Pin Zheng Journal: Neuro Oncol Date: 2014-09-24 Impact factor: 12.300
Authors: Fred H Hochberg; Nadia A Atai; David Gonda; Michael S Hughes; Brolin Mawejje; Leonora Balaj; Robert S Carter Journal: Expert Rev Mol Diagn Date: 2014-05 Impact factor: 5.225
Authors: Carmen Balana; Ramon De Las Penas; Juan Manuel Sepúlveda; Miguel J Gil-Gil; Raquel Luque; Oscar Gallego; Cristina Carrato; Carolina Sanz; Gaspar Reynes; Ana Herrero; Jose Luis Ramirez; Pedro Pérez-Segura; Alfonso Berrocal; Jose Maria Vieitez; Almudena Garcia; Sergio Vazquez-Estevez; Sergi Peralta; Isaura Fernandez; Ivan Henriquez; Maria Martinez-Garcia; Juan Jose De la Cruz; Jaume Capellades; Pilar Giner; Salvador Villà Journal: J Neurooncol Date: 2016-02-03 Impact factor: 4.130