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Clinical correlation of MGMT protein expression and promoter methylation in Chinese glioblastoma patients

Abstract

Promoter methylation of O6-methylguanine-DNA methyltransferase (MGMT) gene has been considered as a prognostic maker and increasingly emphasized in the treatment of glioblastoma multiforme (GBM). Contrastingly, the correlation of MGMT with clinical outcomes in Chinese glioblastoma patients has not been elucidated systematically. In the present study, tumor tissues from 172 GBM patients were analyzed for MGMT protein expression by immunohistochemistry. Of these, 79 were also subjected to pyrosequencing for MGMT promoter methylation analysis. MGMT protein overexpression was found in 109/172 (63.4%) GBM samples. And no significant survival difference was observed between the patients with MGMT overexpression and low expression in terms of progression-free survival or overall survival (P = 0.605 and P = 0.565, respectively). Meanwhile, MGMT promoter methylation was detected in 26/79 cases (32.9%), whereas 53/79 (67.1%) samples were unmethylated. Further survival analysis also revealed that MGMT promoter methylation status cannot predict patients progression-free survival and overall survival (P = 0.906 and P = 0.548, respectively). The integrated analysis showed that there was significant negative correlation between MGMT protein expression and promoter methylation (P = 0.004). These results underscore that, in Chinese GBM patients, (a) MGMT protein expression level was not a prognostic factor, (b) overall survival but not progression-free survival showed a trend toward increase in patients with MGMT promoter methylation, although the difference was not significant statistically and this observation has to be validated in larger patients cohort, (c) there was a significant correlation between MGMT protein expression in immunohistochemistry and MGMT promoter methylation by pyrosequencing.

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References

  1. Clarke J, Butowski N, Chang S. Recent advances in therapy for glioblastoma. Arch Neurol. 2010;67:279–83.

    PubMed  Article  Google Scholar 

  2. Dunn J, et al. Extent of MGMT promoter methylation correlates with outcome in glioblastomas given temozolomide and radiotherapy. Br J Cancer. 2009;101:124–31.

    PubMed  Article  CAS  Google Scholar 

  3. Rivera AL, et al. MGMT promoter methylation is predictive of response to radiotherapy and prognostic in the absence of adjuvant alkylating chemotherapy for glioblastoma. Neuro Oncol. 2010;12:116–21.

    PubMed  Article  CAS  Google Scholar 

  4. Nagane M, Kobayashi K, Ohnishi A, Shimizu S, Shiokawa Y. Prognostic significance of O6-methylguanine-DNA methyltransferase protein expression in patients with recurrent glioblastoma treated with temozolomide. Jpn J Clin Oncol. 2007;37:897–906.

    PubMed  Article  Google Scholar 

  5. Kitange GJ, et al. Evaluation of MGMT promoter methylation status and correlation with temozolomide response in orthotopic glioblastoma xenograft model. J Neurooncol. 2009;92:23–31.

    PubMed  Article  CAS  Google Scholar 

  6. Zhang W, et al. Antiangiogenic therapy with bevacizumab in recurrent malignant gliomas: analysis of the response and core pathway aberrations. Chin Med J (Engl). 2009; 5(122):1250–4.

    Google Scholar 

  7. Nishikawa R. Standard therapy for glioblastoma–a review of where we are. Neurol Med Chir (Tokyo). 2010;50:713–9.

    Article  Google Scholar 

  8. Hegi ME, et al. MGMT gene silencing and benefit from temozolomide in glioblastoma. N Engl J Med. 2005;352:997–1003.

    PubMed  Article  CAS  Google Scholar 

  9. Blanc JL, et al. Correlation of clinical features and methylation status of MGMT gene promoter in glioblastomas. J Neurooncol. 2004;68:275–83.

    PubMed  Article  CAS  Google Scholar 

  10. Brell M, et al. Prognostic significance of O6-methylguanine-DNA methyltransferase determined by promoter hypermethylation and immunohistochemical expression in anaplastic gliomas. Clin Cancer Res. 2005;11:5167–74.

    PubMed  Article  CAS  Google Scholar 

  11. Rodriguez FJ, et al. MGMT immunohistochemical expression and promoter methylation in human glioblastoma. Appl Immunohistochem Mol Morphol. 2008;16:59–65.

    PubMed  CAS  Google Scholar 

  12. Franceschi E, Tosoni A, Pozzati E, Brandes AA. Association between response to primary treatments and MGMT status in glioblastoma. Expert Rev Anticancer Ther. 2008;8:1781–6.

    PubMed  Article  CAS  Google Scholar 

  13. Hegi ME, et al. Correlation of O6-methylguanine methyltransferase (MGMT) promoter methylation with clinical outcomes in glioblastoma and clinical strategies to modulate MGMT activity. J Clin Oncol. 2008;26:4189–99.

    PubMed  Article  CAS  Google Scholar 

  14. van den Bent MJ, et al. MGMT promoter methylation is prognostic but not predictive for outcome to adjuvant PCV chemotherapy in anaplastic oligodendroglial tumors: a report from EORTC Brain Tumor Group Study 26951. J Clin Oncol. 2009;27:5881–6.

    PubMed  Article  Google Scholar 

  15. Hassel JC, et al. MGMT gene promoter methylation correlates with tolerance of temozolomide treatment in melanoma but not with clinical outcome. Br J Cancer. 2010;103:820–6.

    PubMed  Article  CAS  Google Scholar 

  16. Sarkaria JN, et al. Mechanisms of chemoresistance to alkylating agents in malignant glioma. Clin Cancer Res. 2008;14:2900–8.

    PubMed  Article  CAS  Google Scholar 

  17. Everhard S, et al. Identification of regions correlating MGMT promoter methylation and gene expression in glioblastomas. Neuro Oncol. 2009;11:348–56.

    PubMed  Article  CAS  Google Scholar 

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Acknowledgments

This work was Supported by grants from National Key Project of Science and Technology Supporting Programs of China (No.2007BAI05B08) and National Natural Science Foundation of China (No.30772238 and 30730035).

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Correspondence to Tao Jiang.

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Kai Tang and Qiang Jin contributed equally.

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Tang, K., Jin, Q., Yan, W. et al. Clinical correlation of MGMT protein expression and promoter methylation in Chinese glioblastoma patients. Med Oncol 29, 1292–1296 (2012). https://doi.org/10.1007/s12032-011-9901-4

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  • DOI: https://doi.org/10.1007/s12032-011-9901-4

Keywords

  • MGMT
  • Glioblastoma
  • Methylation