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Relationships between recurrence patterns and subventricular zone involvement or CD133 expression in glioblastoma

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Abstract

Introduction

We previously reported that CD133 expression correlated with the recurrence pattern of glioblastoma (GBM). Subventricular zone (SVZ) involvement may also be associated with distant recurrence in GBM. Therefore, we herein investigated whether the combined analysis of SVZ involvement and CD133 expression is useful for predicting the pattern of GBM recurrence.

Materials and methods

We retrospectively analyzed 167 cases of GBM. Tumors were divided into four groups based on spatial relationships between contrast-enhanced lesions (CEL) and the SVZ or cortex (Ctx) on MRI. The initial recurrence pattern (local/distant) was obtained from medical records. To identify factors predictive of recurrence, we examined CD133 expression by immunohistochemical, clinical (age, sex, KPS, Ki-67 labeling index, surgery, and MRI characteristics), and genetic (IDH1, MGMT, and BRAF) factors.

Results

The CD133 expression rate was higher in SVZ-positive tumors than in SVZ-negative tumors (P = 0.046). Distant recurrence was observed in 21% of patients, and no significant difference was noted in recurrence patterns among the four groups. However, strong CD133 expression was associated with a shorter time to distant recurrence in univariate, multivariate, and propensity-matched scoring analyses (P < 0.0001, P = 0.001, and P = 0.0084, respectively). In the combined analysis, distant recurrence was the most frequent (70%) in group III (SVZ-negative, Ctx-positive) GBM and those with high CD133 expression rates (≥ 15%).

Conclusion

An integrated analysis of CD133 expression and MRI-based tumor classification may be useful for predicting the recurrence pattern of GBM.

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Abbreviations

MRI:

Magnetic resonance imaging

OS:

Overall survival

TTD:

Time to distant recurrence

TTL:

Time to local recurrence

IDH:

Isocitrate dehydrogenase

SVZ:

Subventricular zone

Ctx:

Cortex

CEL:

Contrast-enhanced lesions

GBM:

Glioblastoma

NSC:

Neural stem cells

Gd:

Gadolinium

FLAIR:

Fluid-attenuated inversion-recovery

SPGR:

Spoiled gradient-recalled acquisition in the steady state

References

  1. Louis DN, Ohgaki H, Wiestler OD, Cavenee WK, Ellison DW, Figarella-Branger D, Perry A, Reifenberger G, Demiling A (eds) (2016) WHO classification of Tumors of the Central Nervous System, 4th edn. IARC Press, Lyon

    Google Scholar 

  2. 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

    Article  CAS  Google Scholar 

  3. Stummer W, Pichlmeier U, Meinel T, Wiestler OD, Zanella F, Reulen HJ (2006) Fluorescence-guided surgery with 5-aminolevulinic acid for resection of malignant glioma: a randomised controlled multicentre phase III trial. Lancet Oncol 7:392–401

    Article  CAS  Google Scholar 

  4. Senft C, Bink A, Franz K, Vatter H, Gasser T, Seifert V (2011) Intraoperative MRI guidance and extent of resection in glioma surgery: a randomised, controlled trial. Lancet Oncol 12:997–1003

    Article  Google Scholar 

  5. 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

    Article  CAS  Google Scholar 

  6. Endo H, Kumabe T, Jokura H, Shirane R, Ariga H, Takai Y, Yoshimoto T (2003) Leptomeningeal dissemination of cerebellar malignant astrocytomas. J Neurooncol 63:191–199

    Article  Google Scholar 

  7. Kato H, Fujimura M, Kumabe T, Ishioka C, Kanamaru R, Yoshimoto T (2004) PTEN gene mutation and high MIB-1 labeling index may contribute to dissemination in patients with glioblastoma. J Clin Neurosci 11:37–41

    Article  CAS  Google Scholar 

  8. Korshunov A, Sycheva R, Golanov A, Pronin I (2007) Gains at the 1p36 chromosomal region are associated with symptomatic leptomeningeal dissemination of supratentorial glioblastomas. Am J Clin Pathol 127:585–590

    Article  CAS  Google Scholar 

  9. Parsa AT, Wachhorst S, Lamborn KR, Prados MD, McDermott MW, Berger MS, Chang SM (2005) Prognostic significance of intracranial dissemination of glioblastoma multiforme in adults. J Neurosurg 102:622–628

    Article  Google Scholar 

  10. Elliott JP, Keles GE, Waite M, Temkin N, Berger MS (1994) Ventricular entry during resection of malignant gliomas: effect on intracranial cerebrospinal fluid tumor dissemination. J Neurosurg 80:834–839

    Article  CAS  Google Scholar 

  11. Wick W, Stupp R, Beule AC, Bromberg J, Wick A, Ernemann U, Platten M, Marosi C, Mason WP, van den Bent M, Weller M, Rorden C, Karnath HO (2008) A novel tool to analyze MRI recurrence patterns in glioblastoma. Neuro Oncol 10:1019–1024

    Article  Google Scholar 

  12. Reya T, Morrison SJ, Clarke MF, Weissman IL (2001) Stem cells, cancer and cancer stem cells. Nature 414:105–111

    Article  CAS  Google Scholar 

  13. Dean M, Fojo T, Bates S (2005) Tumor stem cells and drug resistance. Nat Rev Cancer 5:275–284

    Article  CAS  Google Scholar 

  14. Lapidot T, Sirard C, Vormoor J, Murdoch B, Hoang T, Caceres-Cortes J, Minden M, Paterson B, Caligiuri MA, Dick JE (1994) A cell initiating human acute myeloid leukaemia after transplantation into SCID mice. Nature 367:645–648

    Article  CAS  Google Scholar 

  15. Singh SK, Clarke ID, Terasaki M, Bonn VE, Hawkins C, Squire J, Dirks PB (2003) Identification of a cancer stem cell in human brain tumors. Cancer Res 63:5821–5828

    CAS  PubMed  Google Scholar 

  16. Sato A, Sakurada K, Kumabe T, Sasajima T, Beppu T, Asano K, Ohkuma H, Ogawa A, Mizoi K, Tominaga T, Kitanaka C, Kayama T (2010) Association of stem cell marker CD133 expression with dissemination of glioblastomas. Neurosurg Rev. 33:175–184

    Article  Google Scholar 

  17. Shibahara I, Sonoda Y, Saito R, Kanamori M, Yamashita Y, Kumabe T, Watanabe M, Suzuki H, Watanabe T, Ishioka C, Tominaga T (2013) The expression status of CD133 is associated with the pattern and timing of primary glioblastoma recurrence. Neurooncology 15:1151–1159

    CAS  Google Scholar 

  18. Altmann C, Keller S, Schmidt MHH (2019) The role of SVZ stem cells in glioblastoma. Cancers (Basel). https://doi.org/10.3390/cancers11040448

    Article  Google Scholar 

  19. Sanai N, Alvarez-Buylla A, Berger MS (2005) Neural stem cells and the origin of gliomas. N Engl J Med 353:811–822

    Article  CAS  Google Scholar 

  20. Chaichana KL, McGirt MJ, Frazier J, Attenello F, Guerrero-Cazares H, Quinones-Hinojosa A (2008) Relationship of glioblastoma multiforme to the lateral ventricles predicts survival following tumor resection. J Neurooncol 89:219–224

    Article  Google Scholar 

  21. Lim DA, Cha S, Mayo MC, Chen MH, Keles E, VandenBerg S, Berger MS (2007) Relationship of glioblastoma multiforme to neural stem cell regions predicts invasive and multifocal tumor phenotype. Neuro Oncol 9:424–429

    Article  Google Scholar 

  22. Jafri NF, Clarke JL, Weinberg V, Barani IJ, Cha S (2013) Relationship of glioblastoma multiforme to the subventricular zone is associated with survival. Neuro Oncol 15:91–96

    Article  CAS  Google Scholar 

  23. Kappadakunnel M, Eskin A, Dong J, Nelson SF, Mischel PS, Liau LM, Ngheimphu P, Lai A, Cloughesy TF, Goldin J, Pope WB (2010) Stem cell associated gene expression in glioblastoma multiforme: relationship to survival and the subventricular zone. J Neurooncol 96:359–367

    Article  CAS  Google Scholar 

  24. Pope WB, Xia Q, Paton VE, Das A, Hambleton J, Kim HJ, Huo J, Brown MS, Goldin J, Cloughesy T (2011) Patterns of progression in patients with recurrent glioblastoma treated with bevacizumab. Neurology 76:432–437

    Article  CAS  Google Scholar 

  25. Cachia D, Elshafeey NA, Kamiya-Matsuoka C, Hatami M, Alfaro-Munoz KD, Mandel JJ, Colen R, DeGroot JF (2017) Radiographic patterns of progression with associated outcomes after bevacizumab therapy in glioblastoma patients. J Neurooncol 135:75–81

    Article  CAS  Google Scholar 

  26. 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

    Article  CAS  Google Scholar 

  27. Schindler G, Capper D, Meyer J, Janzarik W, Omran H, Herold-Mende C, Schmieder K, Wesseling P, Mawrin C, Hasselblatt M, Louis DN, Korshunov A, Pfister S, Hartmann C, Paulus W, Reifenberger G, von Deimling A (2011) Analysis of BRAF V600E mutation in 1320 nervous system tumors reveals high mutation frequencies in pleomorphic xanthoastrocytoma, ganglioglioma and extra-cerebellar pilocytic astrocytoma. Acta Neuropathol 121:397–405

    Article  CAS  Google Scholar 

  28. Sasaki T, Fukai J, Kodama Y, Hirose T, Okita Y, Moriuchi S, Nonaka M, Tsuyuguchi N, Terakawa Y, Uda T, Tomogane Y, Kinoshita M, Nishida N, Izumoto S, Nakajima Y, Arita H, Ishibashi K, Shofuda T, Kanematsu D, Yoshioka E, Mano M, Fujita K, Uematsu Y, Nakao N, Mori K, Kanemura Y (2018) Characteristics and outcomes of elderly patients with diffuse gliomas: a multi-institutional cohort study by Kansai Molecular Diagnosis Network for CNS Tumors. J Neurooncol 140:329–339

    Article  Google Scholar 

  29. Lee JH, Lee JE, Kahng JY, Kim SH, Park JS, Yoon SJ, Um JY, Kim WK, Lee JK, Park J, Kim EH, Lee JH, Lee JH, Chung WS, Ju YS, Park SH, Chang JH, Kang SG, Lee JH (2018) Human glioblastoma arises from subventricular zone cells with low-level driver mutations. Nature 560(7717):243–247

    Article  CAS  Google Scholar 

  30. Nitta M, Muragaki Y, Maruyama T, Iseki H, Komori T, Ikuta S, Saito T, Yasuda T, Hosono J, Okamoto S, Koriyama S, Kawamata T (2018) Role of photodynamic therapy using talaporfin sodium and a semiconductor laser in patients with newly diagnosed glioblastoma. J Neurosurg 1:1–8. https://doi.org/10.3171/2018.7.JNS18422

    Article  Google Scholar 

  31. Bernstock JD, Mooney JH, Ilyas A, Chagoya G, Estevez-Ordonez D, Ibrahim A, Nakano I (2019) Molecular and cellular intratumoral heterogeneity in primary glioblastoma: clinical and translational implications. J Neurosurg 23:1–9. https://doi.org/10.3171/2019.5.JNS19364

    Article  Google Scholar 

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Acknowledgements

We thank Yanagida S. and Sugawara M. for their assistance in extracting genomic DNA and in obtaining MR images. The authors thank Medical English Service (www.med-english.com) for the English language review.

Funding

This work was supported by JSPS KAKENHI Grant Number 17K10856.

Author information

Authors and Affiliations

  1. Department of Neurosurgery, Faculty of Medicine, Yamagata University, 2-2 Iida-Nishi, Yamagata, Yamagata, 990-9585, Japan

    Tetsu Yamaki, Ken-ichiro Matsuda & Yukihiko Sonoda

  2. Department of Neurosurgery, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan

    Ichiyo Shibahra

  3. Department of Biomedical Research and Innovation, Institute for Clinical Research, National Hospital Organization Osaka National Hospital, Osaka, Japan

    Yonehiro Kanemura

  4. Department of Public Health, Faculty of Medicine, Yamagata University, Yamagata, Yamagata, Japan

    Tsuneo Konta

  5. Department of Neurosurgery, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan

    Masayuki Kanamori & Teiji Tominaga

  6. Department of Pathology, Faculty of Medicine, Yamagata University, Yamagata, Yamagata, Japan

    Mitsunori Yamakawa

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  1. Tetsu Yamaki
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Correspondence to Yukihiko Sonoda.

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Yamaki, T., Shibahra, I., Matsuda, Ki. et al. Relationships between recurrence patterns and subventricular zone involvement or CD133 expression in glioblastoma. J Neurooncol 146, 489–499 (2020). https://doi.org/10.1007/s11060-019-03381-y

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  • DOI: https://doi.org/10.1007/s11060-019-03381-y

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