MGMT promoter methylation status and MGMT and CD133 immunohistochemical expression as prognostic markers in glioblastoma patients treated with temozolomide plus radiotherapy

Journal of Translational Medicine

Research

Angel Concha¹  Rodrigo López¹  Roberto Madeddu²  Pablo Juan Alvarez³  Jaime Antonio Oliver³  Gloria Perazzoli³  Consolación Melguizo⁴  Antonia Aránega⁴  Jose Prados⁴  Fernando Rodríguez-Serrano⁴  Raul Ortiz⁵  Beatriz González⁶ 

[1] Anatomopathological Service, Virgen de las Nieves Hospital, 18014, Granada, Spain;Departament of Biomedical Science - Histology, University of Sassari, Sassari, Italy;National Institute of Biostructures and Biosystems, INBB, Sassari, Italy;Institute of Biopathology and Regenerative Medicine (IBIMER), 18100, Granada, Spain;Institute of Biopathology and Regenerative Medicine (IBIMER), 18100, Granada, Spain;Department of Anatomy and Embriology, University of Granada, 18012, Granada, Spain;Institute of Biopathology and Regenerative Medicine (IBIMER), 18100, Granada, Spain;Department of Health Science, University of Jaén, 23071, Jaén, Spain;Service of Medical Oncology, Virgen de las Nieves Hospital, 18014, Granada, Spain;

关键词: Glioblastoma;    Radiotherapy;    Temozolomide;    MGMT;    Methylation;    CD133;   

DOI  :  10.1186/1479-5876-10-250

 received in 2012-10-21, accepted in 2012-12-10,  发布年份 2012

来源: Springer

【 摘 要 】

BackgroundThe CD133 antigen is a marker of radio- and chemo-resistant stem cell populations in glioblastoma (GBM). The O6-methylguanine DNA methyltransferase (MGMT) enzyme is related with temozolomide (TMZ) resistance. Our propose is to analyze the prognostic significance of the CD133 antigen and promoter methylation and protein expression of MGMT in a homogenous group of GBM patients uniformly treated with radiotherapy and TMZ. The possible connection between these GBM markers was also investigated.MethodsSeventy-eight patients with GBM treated with radiotherapy combined with concomitant and adjuvant TMZ were analyzed for MGMT and CD133. MGMT gene promoter methylation was determined by methylation-specific polymerase chain reaction after bisulfite treatment. MGMT and CD133 expression was assessed immunohistochemically using an automatic quantification system. Overall and progression-free survival was calculated according to the Kaplan–Meier method.ResultsThe MGMT gene promoter was found to be methylated in 34 patients (44.7%) and unmethylated in 42 patients (55.3%). A significant correlation was observed between MGMT promoter methylation and patients’ survival. Among the unmethylated tumors, 52.4% showed low expression of MGMT and 47.6% showed high-expression. Among methylated tumors, 58.8% showed low-expression of MGMT and 41.2% showed high-expression. No correlation was found between MGMT promoter methylation and MGMT expression, or MGMT expression and survival. In contrast with recent results, CD133 expression was not a predictive marker in GBM patients. Analyses of possible correlation between CD133 expression and MGMT protein expression or MGMT promoter methylation were negative.ConclusionsOur results support the hypothesis that MGMT promoter methylation status but not MGMT expression may be a predictive biomarker in the treatment of patients with GBM. In addition, CD133 should not be used for prognostic evaluation of these patients. Future studies will be necessary to determine its clinical utility.

【 授权许可】

Unknown   
© Melguizo et al.; licensee BioMed Central Ltd. 2012. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.