Vol 53, No 6 (2019)
Research Paper
Published online: 2019-11-20

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Biomarker concordance between molecular stereotactic biopsy and open surgical specimens in gliomas

Jacek Furtak1, Maciej Mielczarek1, Mateusz Szylberg1, Maciej Harat2
Pubmed: 31746452
Neurol Neurochir Pol 2019;53(6):435-441.


Aims. To compare 1p/19q codeletion, MGMT promoter methylation, and IDH mutation status in stereotactic biopsy and open craniotomy specimens.

Clinical rationale. The latest WHO classification of gliomas requires assessment of the expression of molecular markers. Samples can be obtained for molecular assays via open craniotomy or molecular stereotactic biopsy (MSB). However, there is uncertainty as to whether MSB is representative of the entire tumour, and therefore how reliable it is for treatment planning.

Patients and methods. We examined 11 patients diagnosed with brain tumours suspicious of glioma who underwent open craniotomy after stereotactic biopsy and in whom multiple biomarkers were assessed in both sets of samples by methylation-specific multiplex ligation-dependent probe amplification. Institutional Review Board ethical approval was granted (KB 694/2018).

Results. The initial histopathological grade as determined by stereotactic biopsy was the same as in the samples obtained by open surgery. Further, the marker profile used here was valid in both high- and low-grade gliomas.

Conclusion and clinical implication. MSB is a reliable way to obtain material for precision medicine approaches.

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  1. Fisher J, Schwartzbaum J, Wrensch M, et al. Epidemiology of Brain Tumors. Neurologic Clinics. 2007; 25(4): 867–890.
  2. Louis DN, Ohgaki H, Wiestler OD, et al. The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathol. 2007; 114(2): 97–109.
  3. Ostrom QT, Gittleman H, Truitt G, et al. CBTRUS Statistical Report: Primary Brain and Other Central Nervous System Tumors Diagnosed in the United States in 2011-2015. Neuro Oncol. 2018; 20(suppl_4): iv1–iv86.
  4. Sathornsumetee S, Rich JN, Reardon DA. Diagnosis and treatment of high-grade astrocytoma. Neurol Clin. 2007; 25(4): 1111–1139, x.
  5. Weller M, Pfister SM, Wick W, et al. Molecular neuro-oncology in clinical practice: a new horizon. Lancet Oncol. 2013; 14(9): e370–e379.
  6. Wen PY, Kesari S. Malignant gliomas in adults. N Engl J Med. 2008; 359(5): 492–507.
  7. Brat DJ, Verhaak RGW, Aldape KD, et al. Cancer Genome Atlas Research Network. Comprehensive, Integrative Genomic Analysis of Diffuse Lower-Grade Gliomas. N Engl J Med. 2015; 372(26): 2481–2498.
  8. Dubbink HJ, Atmodimedjo PN, Kros JM, et al. Molecular classification of anaplastic oligodendroglioma using next-generation sequencing: a report of the prospective randomized EORTC Brain Tumor Group 26951 phase III trial. Neuro Oncol. 2016; 18(3): 388–400.
  9. Eckel-Passow JE, Lachance DH, Molinaro AM, et al. Glioma Groups Based on 1p/19q, IDH, and TERT Promoter Mutations in Tumors. N Engl J Med. 2015; 372(26): 2499–2508.
  10. Hegi ME, Stupp R. Withholding temozolomide in glioblastoma patients with unmethylated MGMT promoter--still a dilemma? Neuro Oncol. 2015; 17(11): 1425–1427.
  11. Goldstein ED, Feyissa AM. Brain tumor related-epilepsy. Neurol Neurochir Pol. 2018; 52(4): 436–447.
  12. Horbinski C. What do we know about IDH1/2 mutations so far, and how do we use it? Acta Neuropathol. 2013; 125(5): 621–636.
  13. Hartmann C, Mueller W, Lass U, et al. Molecular genetic analysis of oligodendroglial tumors. J Neuropathol Exp Neurol. 2005; 64(1): 10–14.
  14. Okamoto Y, Di Patre PL, Burkhard C, et al. Population-based study on incidence, survival rates, and genetic alterations of low-grade diffuse astrocytomas and oligodendrogliomas. Acta Neuropathol. 2004; 108(1): 49–56.
  15. Appin CL, Gao J, Chisolm C, et al. Glioblastoma with oligodendroglioma component (GBM-O): molecular genetic and clinical characteristics. Brain Pathol. 2013; 23(4): 454–461.
  16. Eigenbrod S, Trabold R, Brucker D, et al. Molecular stereotactic biopsy technique improves diagnostic accuracy and enables personalized treatment strategies in glioma patients. Acta Neurochir (Wien). 2014; 156(8): 1427–1440.
  17. Iuchi T, Namba H, Iwadate Y, et al. Identification of the small interstitial deletion at chromosome band 1p34-p35 and its association with poor outcome in oligodendroglial tumors. Genes Chromosomes Cancer. 2002; 35(2): 170–175.
  18. Louis D, Ohgaki H, Wiestler O, et al. The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathologica. 2007; 114(5): 547–547.
  19. Weise LM, Harter PN, Eibach S, et al. Confounding factors in diagnostics of MGMT promoter methylation status in glioblastomas in stereotactic biopsies. Stereotact Funct Neurosurg. 2014; 92(3): 129–139.
  20. Jeuken JWM, Cornelissen SJB, Vriezen M, et al. MS-MLPA: an attractive alternative laboratory assay for robust, reliable, and semiquantitative detection of MGMT promoter hypermethylation in gliomas. Lab Invest. 2007; 87(10): 1055–1065.
  21. Franco-Hernández C, Martínez-Glez V, de Campos JM, et al. Allelic status of 1p and 19q in oligodendrogliomas and glioblastomas: multiplex ligation-dependent probe amplification versus loss of heterozygosity. Cancer Genet Cytogenet. 2009; 190(2): 93–96.
  22. Natté R, Eijk R, Eilers P, et al. Multiplex Ligation-Dependent Probe Amplification for the Detection of 1p and 19q Chromosomal Loss in Oligodendroglial Tumors. Brain Pathology. 2006; 15(3): 192–197.
  23. Woehrer A, Hainfellner JA. Molecular diagnostics: techniques and recommendations for 1p/19q assessment. CNS Oncol. 2015; 4(5): 295–306.
  24. Gessler F, Forster MT, Duetzmann S, et al. Combination of Intraoperative Magnetic Resonance Imaging and Intraoperative Fluorescence to Enhance the Resection of Contrast Enhancing Gliomas. Neurosurgery. 2015; 77(1): 16–22; discussion 22.
  25. Lacroix M, Abi-Said D, Fourney DR, et al. A multivariate analysis of 416 patients with glioblastoma multiforme: prognosis, extent of resection, and survival. J Neurosurg. 2001; 95(2): 190–198.
  26. Ringel F, Pape H, Sabel M, et al. SN1 study group. Clinical benefit from resection of recurrent glioblastomas: results of a multicenter study including 503 patients with recurrent glioblastomas undergoing surgical resection. Neuro Oncol. 2016; 18(1): 96–104.
  27. Sanai N, Polley MY, McDermott MW, et al. An extent of resection threshold for newly diagnosed glioblastomas. J Neurosurg. 2011; 115(1): 3–8.
  28. Stupp R, Mason WP, van den Bent MJ, et al. European Organisation for Research and Treatment of Cancer Brain Tumor and Radiotherapy Groups, National Cancer Institute of Canada Clinical Trials Group. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005; 352(10): 987–996.
  29. Nobusawa S, Watanabe T, Kleihues P, et al. IDH1 mutations as molecular signature and predictive factor of secondary glioblastomas. Clin Cancer Res. 2009; 15(19): 6002–6007.
  30. Schumacher T, Bunse L, Pusch S, et al. A vaccine targeting mutant IDH1 induces antitumour immunity. Nature. 2014; 512(7514): 324–327.
  31. Molenaar RJ, Verbaan D, Lamba S, et al. The combination of IDH1 mutations and MGMT methylation status predicts survival in glioblastoma better than either IDH1 or MGMT alone. Neuro Oncol. 2014; 16(9): 1263–1273.
  32. Catapano G, Sgulò FG, Seneca V, et al. Fluorescein-Guided Surgery for High-Grade Glioma Resection: An Intraoperative "Contrast-Enhancer". World Neurosurg. 2017; 104: 239–247.
  33. Bieńkowski M, Wöhrer A, Moser P, et al. Molecular diagnostic testing of diffuse gliomas in the real-life setting: A practical approach. Clin Neuropathol. 2018; 37(4): 166–177.
  34. Harat M, Blok M, Harat A, et al. The impact of adjuvant radiotherapy on molecular prognostic markers in gliomas. Onco Targets Ther. 2019; 12: 2215–2224.
  35. Park CK, Kim JaE, Kim JiY, et al. The Changes in MGMT Promoter Methylation Status in Initial and Recurrent Glioblastomas. Transl Oncol. 2012; 5(5): 393–397.
  36. Barresi V, Caffo M, Luca GDe, et al. O-6-methylguanine-DNA methyltransferase promoter methylation can change in glioblastoma recurrence due to intratumor heterogeneity. Glioma. 2018; 1(6): 208.
  37. Eskilsson E, Rosland GV, Talasila KM, et al. EGFRvIII mutations can emerge as late and heterogenous events in glioblastoma development and promote angiogenesis through Src activation. Neuro Oncol. 2016; 18(12): 1644–1655.
  38. Grasbon-Frodl EM, Kreth FW, Ruiter M, et al. Intratumoral homogeneity of MGMT promoter hypermethylation as demonstrated in serial stereotactic specimens from anaplastic astrocytomas and glioblastomas. Int J Cancer. 2007; 121(11): 2458–2464.
  39. Patel AP, Tirosh I, Trombetta JJ, et al. Single-cell RNA-seq highlights intratumoral heterogeneity in primary glioblastoma. Science. 2014; 344(6190): 1396–1401.
  40. Sciuscio D, Diserens AC, van Dommelen K, et al. Extent and patterns of MGMT promoter methylation in glioblastoma- and respective glioblastoma-derived spheres. Clin Cancer Res. 2011; 17(2): 255–266.
  41. Sottoriva A, Kang H, Ma Z, et al. A Big Bang model of human colorectal tumor growth. Nat Genet. 2015; 47(3): 209–216.
  42. Parker NR, Hudson AL, Khong P, et al. Intratumoral heterogeneity identified at the epigenetic, genetic and transcriptional level in glioblastoma. Sci Rep. 2016; 6: 22477.
  43. Parkinson JF, Wheeler HR, Clarkson A, et al. Variation of O(6)-methylguanine-DNA methyltransferase (MGMT) promoter methylation in serial samples in glioblastoma. J Neurooncol. 2008; 87(1): 71–78.
  44. Kunz M, Thon N, Eigenbrod S, et al. Hot spots in dynamic (18)FET-PET delineate malignant tumor parts within suspected WHO grade II gliomas. Neuro Oncol. 2011; 13(3): 307–316.
  45. Gessler F, Baumgarten P, Bernstock JD, et al. Assessment of molecular markers demonstrates concordance between samples acquired via stereotactic biopsy and open craniotomy in both anaplastic astrocytomas and glioblastomas. J Neurooncol. 2017; 133(2): 399–407.
  46. Aker F, Hakan T, Karadereler S, et al. Accuracy and diagnostic yield of stereotactic biopsy in the diagnosis of brain masses: Comparison of results of biopsy and resected surgical specimens. Neuropathology. 2005; 25(3): 207–213.
  47. Jain D, Sharma MC, Sarkar C, et al. Correlation of diagnostic yield of stereotactic brain biopsy with number of biopsy bits and site of the lesion. Brain Tumor Pathol. 2006; 23(2): 71–75.
  48. Shastri-Hurst N, Tsegaye M, Robson DK, et al. Stereotactic brain biopsy: An audit of sampling reliability in a clinical case series. Br J Neurosurg. 2006; 20(4): 222–226.
  49. Smith JS, Quiñones-Hinojosa A, Barbaro NM, et al. Frame-based stereotactic biopsy remains an important diagnostic tool with distinct advantages over frameless stereotactic biopsy. J Neurooncol. 2005; 73(2): 173–179.
  50. Weise LM, Bruder M, Eibach S, et al. Efficacy and safety of local versus general anesthesia in stereotactic biopsies: a matched-pairs cohort study. J Neurosurg Anesthesiol. 2013; 25(2): 148–153.
  51. Gessler F, Bruder M, Duetzmann S, et al. Risk factors governing the development of cerebral vein and dural sinus thrombosis after craniotomy in patients with intracranial tumors. J Neurosurg. 2018; 128(2): 373–379.

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