Abstract
The purpose of this study was to distinguish pseudoprogression (PP) from early true progression in patients with glioblastoma (GBM) based on the presence of a mutation in isocitrate dehydrogenase 1 (IDH1). We retrospectively surveyed 32 patients with GBM or GBM with oligodendroglioma component (GBMO) who underwent biopsy or maximal tumor resection followed by concurrent radiotherapy and temozolomide (TMZ). We then selected patients with early radiological progression in magnetic resonance imaging within 6Â months after concurrent radiotherapy and TMZ treatment. DNA was extracted from their tumor blocks. The IDH1 mutation was analyzed in the genomic region by direct sequencing as a biomarker for PP. Twenty-eight patients were diagnosed with GBM and four with GBMO. Eleven patients were discovered to have early radiological progression. PP was detected in two patients (6.3Â %) diagnosed with GBMO and one patient with GBM. Both of the GBMO patients with PP had the IDH1 mutation, the one GBM patient with PP and the other eight patients with early true progression with wild type. The sensitivity and specificity of the IDH1 mutation for detecting PP were 66.7 and 100Â %, respectively. This study suggests the IDH1 mutation may become a novel molecular biomarker for PP. Analyzing the IDH1 mutation, in the case of recognizing early radiological progression, may enable distinction of PP from early true progression, and we could determine the need for second-look surgery.
Similar content being viewed by others
References
Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, Belanger K, Brandes AA, Marosi C, Bogdahn U, Curschmann J, Janzer RC, Ludwin SK, Gorlia T, Allgeier A, Lacombe D, Cairncross JG, Eisenhauer E, Mirimanoff RO (2005) Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 352:987–996
Hygino da Cruz LC, Jr., Rodriguez I, Domingues RC, Gasparetto EL, Sorensen AG (2011) Pseudoprogression and pseudoresponse: imaging challenges in the assessment of posttreatment glioma. AJNR Am J Neuroradiol 32:1978–1985
Parsons DW, Jones S, Zhang X, Lin JC, Leary RJ, Angenendt P, Mankoo P, Carter H, Siu IM, Gallia GL, Olivi A, McLendon R, Rasheed BA, Keir S, Nikolskaya T, Nikolsky Y, Busam DA, Tekleab H, Diaz LA Jr, Hartigan J, Smith DR, Strausberg RL, Marie SK, Shinjo SM, Yan H, Riggins GJ, Bigner DD, Karchin R, Papadopoulos N, Parmigiani G, Vogelstein B, Velculescu VE, Kinzler KW (2008) An integrated genomic analysis of human glioblastoma multiforme. Science 321:1807–1812
Sonoda Y, Kumabe T, Nakamura T, Saito R, Kanamori M, Yamashita Y, Suzuki H, Tominaga T (2009) Analysis of IDH1 and IDH2 mutations in Japanese glioma patients. Cancer Sci 100:1996–1998
Topkan E, Topuk S, Oymak E, Parlak C, Pehlivan B (2012) Pseudoprogression in patients with glioblastoma multiforme after concurrent radiotherapy and temozolomide. Am J Clin Oncol 35:284–289
Hegi ME, Diserens AC, Gorlia T, Hamou MF, de Tribolet N, Weller M, Kros JM, Hainfellner JA, Mason W, Mariani L, Bromberg JE, Hau P, Mirimanoff RO, Cairncross JG, Janzer RC, Stupp R (2005) MGMT gene silencing and benefit from temozolomide in glioblastoma. N Engl J Med 352:997–1003
Hoffman WF, Levin VA, Wilson CB (1979) Evaluation of malignant glioma patients during the postirradiation period. J Neurosurg 50:624–628
Brandes AA, Franceschi E, Tosoni A, Blatt V, Pession A, Tallini G, Bertorelle R, Bartolini S, Calbucci F, Andreoli A, Frezza G, Leonardi M, Spagnolli F, Ermani M (2008) MGMT promoter methylation status can predict the incidence and outcome of pseudoprogression after concomitant radiochemotherapy in newly diagnosed glioblastoma patients. J Clin Oncol 26:2192–2197
Brandes AA, Tosoni A, Spagnolli F, Frezza G, Leonardi M, Calbucci F, Franceschi E (2008) Disease progression or pseudoprogression after concomitant radiochemotherapy treatment: pitfalls in neurooncology. Neuro Oncol 10:361–367
Brandsma D, van den Bent MJ (2009) Pseudoprogression and pseudoresponse in the treatment of gliomas. Curr Opin Neurol 22:633–638
Chaskis C, Neyns B, Michotte A, De Ridder M, Everaert H (2009) Pseudoprogression after radiotherapy with concurrent temozolomide for high-grade glioma: clinical observations and working recommendations. Surg Neurol 72:423–428
Chamberlain MC (2008) Pseudoprogression in glioblastoma. J Clin Oncol 26:4359. author reply 4359–4360
Kang HC, Kim CY, Han JH, Choe GY, Kim JH, Kim IA (2011) Pseudoprogression in patients with malignant gliomas treated with concurrent temozolomide and radiotherapy: potential role of p53. J Neurooncol 102:157–162
Park CK, Kim J, Yim SY, Lee AR, Han JH, Kim CY, Park SH, Kim TM, Lee SH, Choi SH, Kim SK, Kim DG, Jung HW (2011) Usefulness of MS-MLPA for detection of MGMT promoter methylation in the evaluation of pseudoprogression in glioblastoma patients. Neuro Oncol 13:195–202
de Wit MC, de Bruin HG, Eijkenboom W, Sillevis Smitt PA, van den Bent MJ (2004) Immediate post-radiotherapy changes in malignant glioma can mimic tumor progression. Neurology 63:535–537
Wong CS, Van der Kogel AJ (2004) Mechanisms of radiation injury to the central nervous system: implications for neuroprotection. Mol Interv 4:273–284
Wang R, Chadalavada K, Wilshire J, Kowalik U, Hovinga KE, Geber A, Fligelman B, Leversha M, Brennan C, Tabar V (2010) Glioblastoma stem-like cells give rise to tumour endothelium. Nature 468:829–833
Acknowledgments
We thank Yumiko Shinohe for assistance with the preparation of paraffin-embedded tissues and the DNA extraction.
Conflict of interest
None declared.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Motegi, H., Kamoshima, Y., Terasaka, S. et al. IDH1 mutation as a potential novel biomarker for distinguishing pseudoprogression from true progression in patients with glioblastoma treated with temozolomide and radiotherapy. Brain Tumor Pathol 30, 67–72 (2013). https://doi.org/10.1007/s10014-012-0109-x
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10014-012-0109-x