Double-labelling immunohistochemistry for MGMT and a "cocktail" of non-tumourous elements is a reliable, quick and easy technique for inferring methylation status in glioblastomas and other primary brain tumours

Acta Neuropathologica Communications

Volumn 2, Issue 1, 2014, Pages

  Burke, Elinor ^a   Grobler, Mariana ^a   Elderfield, Kay ^a   Bond, Frances ^a   Crocker, Matthew ^a   Taylor, Rohan ^a   Bridges, Leslie R ^a  

^a ST GEORGE S HOSPITAL   (United Kingdom)

Author keywords

Biomarker; Cocktail; Double labelling; Glioblastoma; Glioma; Immunohistochemistry; Methylation; MGMT; MLPA

Indexed keywords

EID: 85005846703     PISSN: None     EISSN: 20515960     Source Type: Journal    
DOI: 10.1186/2051-5960-1-22     Document Type: Article

References (24)

1. Gorlia T, van den Bent MJ, Hegi ME, Mirimanoff RO, Weller M, Cairncross JG, Eisenhauer E, Belanger K, Brandes AA, Allgeier A, et al.: Nomograms for predicting survival of patients with newly diagnosed glioblastoma: prognostic factor analysis of EORTC and NCIC trial 26981-22981/CE.3. Lancet Oncol 2008, 9: 29-38. 10.1016/S1470-2045(07)70384-4
2. Hegi ME, Diserens AC, Godard S, Dietrich PY, Regli L, Ostermann S, Otten P, Van MG, De TN, Stupp R: Clinical trial substantiates the predictive value of O-6-methylguanine-DNA methyltransferase promoter methylation in glioblastoma patients treated with temozolomide. Clin Cancer Res 2004, 10: 1871-1874. 10.1158/1078-0432.CCR-03-0384
3. Herrlinger U, Rieger J, Koch D, Loeser S, Blaschke B, Kortmann RD, Steinbach JP, Hundsberger T, Wick W, Meyermann R, et al.: Phase II trial of lomustine plus temozolomide chemotherapy in addition to radiotherapy in newly diagnosed glioblastoma: UKT-03. J Clin Oncol 2006, 24: 4412-4417. 10.1200/JCO.2006.06.9104
4. Stupp R, Hegi ME, Mason WP, van den Bent MJ, Taphoorn MJ, Janzer RC, Ludwin SK, Allgeier A, Fisher B, Belanger K, et al.: Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial. Lancet Oncol 2009, 10: 459-466. 10.1016/S1470-2045(09)70025-7
5. Quillien V, Lavenu A, Karayan-Tapon L, Carpentier C, Labussiere M, Lesimple T, Chinot O, Wager M, Honnorat J, Saikali S, et al.: Comparative assessment of 5 methods (methylation-specific polymerase chain reaction, MethyLight, pyrosequencing, methylation-sensitive high-resolution melting, and immunohistochemistry) to analyze O6-methylguanine-DNA-methyltranferase in a series of 100 glioblastoma patients. Cancer 2012, 118: 4201-4211. 10.1002/cncr.27392
6. Preusser M, Charles JR, Felsberg J, Reifenberger G, Hamou MF, Diserens AC, Stupp R, Gorlia T, Marosi C, Heinzl H, et al.: Anti-O6-methylguanine-methyltransferase (MGMT) immunohistochemistry in glioblastoma multiforme: observer variability and lack of association with patient survival impede its use as clinical biomarker. Brain Pathol 2008, 18: 520-532.
7. Nakasu S, Fukami T, Baba K, Matsuda M: Immunohistochemical study for O6-methylguanine-DNA methyltransferase in the non-neoplastic and neoplastic components of gliomas. J Neurooncol 2004, 70: 333-340. 10.1007/s11060-004-9170-6
8. Stupp R, Hegi ME: Methylguanine methyltransferase testing in glioblastoma: when and how? J Clin Oncol 2007, 25: 1459-1460. 10.1200/JCO.2006.09.7139
9. Watanabe R, Nakasu Y, Tashiro H, Mitsuya K, Ito I, Nakasu S, Nakajima T: O6-methylguanine DNA methyltransferase expression in tumor cells predicts outcome of radiotherapy plus concomitant and adjuvant temozolomide therapy in patients with primary glioblastoma. Brain Tumor Pathol 2011, 28: 127-135. 10.1007/s10014-011-0022-8
10. Jeuken JW, Cornelissen SJ, Vriezen M, Dekkers MM, Errami A, Sijben A, Boots-Sprenger SH, Wesseling P: MS-MLPA: an attractive alternative laboratory assay for robust, reliable, and semiquantitative detection of MGMT promoter hypermethylation in gliomas. Lab Invest 2007, 87: 1055-1065. 10.1038/labinvest.3700664
11. Brell M, Tortosa A, Verger E, Gil JM, Vinolas N, Villa S, Acebes JJ, Caral L, Pujol T, Ferrer I, et al.: Prognostic significance of O6-methylguanine-DNA methyltransferase determined by promoter hypermethylation and immunohistochemical expression in anaplastic gliomas. Clin Cancer Res 2005, 11: 5167-5174. 10.1158/1078-0432.CCR-05-0230
12. Kreth S, Thon N, Eigenbrod S, Lutz J, Ledderose C, Egensperger R, Tonn JC, Kretzschmar HA, Hinske LC, Kreth FW: O-methylguanine-DNA methyltransferase (MGMT) mRNA expression predicts outcome in malignant glioma independent of MGMT promoter methylation. PLoS One 2011, 6: e17156. 10.1371/journal.pone.0017156
13. Kreth S, Limbeck E, Hinske LC, Schutz SV, Thon N, Hoefig K, Egensperger R, Kreth FW: In human glioblastomas transcript elongation by alternative polyadenylation and miRNA targeting is a potent mechanism of MGMT silencing. Acta Neuropathol 2013, 125: 671-681. 10.1007/s00401-013-1081-1
14. Uno M, Oba-Shinjo SM, Camargo AA, Moura RP, Aguiar PH, Cabrera HN, Begnami M, Rosemberg S, Teixeira MJ, Marie SK: Correlation of MGMT promoter methylation status with gene and protein expression levels in glioblastoma. Clinics (Sao Paulo) 2011, 66: 1747-1755. 10.1590/S1807-59322011001000013
15. Pollack IF, Hamilton RL, Sobol RW, Burnham J, Yates AJ, Holmes EJ, Zhou T, Finlay JL: O6-methylguanine-DNA methyltransferase expression strongly correlates with outcome in childhood malignant gliomas: results from the CCG-945 Cohort. J Clin Oncol 2006, 24: 3431-3437. 10.1200/JCO.2006.05.7265
16. Lalezari S, Chou AP, Tran A, Solis OE, Khanlou N, Chen W, Li S, Carrillo JA, Chowdhury R, Selfridge J, et al.: Combined analysis of O6-methylguanine-DNA methyltransferase protein expression and promoter methylation provides optimized prognostication of glioblastoma outcome. Neuro Oncol 2013, 15: 370-381. 10.1093/neuonc/nos308
17. Cao VT, Jung TY, Jung S, Jin SG, Moon KS, Kim IY, Kang SS, Park CS, Lee KH, Chae HJ: The correlation and prognostic significance of MGMT promoter methylation and MGMT protein in glioblastomas. Neurosurgery 2009, 65: 866-875. 10.1227/01.NEU.0000357325.90347.A1
18. Ingold B, Schraml P, Heppner FL, Moch H: Homogeneous MGMT immunoreactivity correlates with an unmethylated MGMT promoter status in brain metastases of various solid tumors. PLoS One 2009, 4: e4775. 10.1371/journal.pone.0004775
19. Tuominen VJ, Ruotoistenmaki S, Viitanen A, Jumppanen M, Isola J: ImmunoRatio: a publicly available web application for quantitative image analysis of estrogen receptor (ER), progesterone receptor (PR), and Ki-67. Breast Cancer Res 2010, 12: R56. 10.1186/bcr2615
20. Burke E, Grobler M, Elderfield K, Butler S, Taylor R, Crocker M, Bridges LR: Computerized image analysis in the assessment of MGMT immunostaining. Neuropathol Appl Neurobiol 2012,38(Suppl. 1):30-31.
21. Chinot OL, Barrie M, Fuentes S, Eudes N, Lancelot S, Metellus P, Muracciole X, Braguer D, Ouafik L, Martin PM, et al.: Correlation between O6-methylguanine-DNA methyltransferase and survival in inoperable newly diagnosed glioblastoma patients treated with neoadjuvant temozolomide. J Clin Oncol 2007, 25: 1470-1475. 10.1200/JCO.2006.07.4807
22. Capper D, Mittelbronn M, Meyermann R, Schittenhelm J: Pitfalls in the assessment of MGMT expression and in its correlation with survival in diffuse astrocytomas: proposal of a feasible immunohistochemical approach. Acta Neuropathol 2008, 115: 249-259. 10.1007/s00401-007-0310-x
23. Rodriguez FJ, Thibodeau SN, Jenkins RB, Schowalter KV, Caron BL, O'Neill BP, James CD, Passe S, Slezak J, Giannini C: MGMT immunohistochemical expression and promoter methylation in human glioblastoma. Appl Immunohistochem Mol Morphol 2008, 16: 59-65.
24. Karayan-Tapon L, Quillien V, Guilhot J, Wager M, Fromont G, Saikali S, Etcheverry A, Hamlat A, Loussouarn D, Campion L, et al.: Prognostic value of O6-methylguanine-DNA methyltransferase status in glioblastoma patients, assessed by five different methods. J Neurooncol 2010, 97: 311-322. 10.1007/s11060-009-0031-1