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The clinicopathological analysis of receptor tyrosine kinases in meningiomas: the expression of VEGFR-2 in meningioma was associated with a higher WHO grade and shorter progression-free survival

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Abstract

WHO grade II/III meningiomas recur frequently and there is currently no established molecular target therapy for meningioma. No previous studies have revealed the association between receptor tyrosine kinases (RTKs) and the recurrence of meningiomas. This study aims to elucidate the association between RTKs and the clinicopathological characteristics and recurrence of meningioma. We investigated the immunohistochemical expression of RTKs (VEGFR-1/2/3, PDGFR-alpha/beta and c-Kit) in 81 meningiomas (WHO grade I, n = 64, WHO grade II/III, n = 17) in 74 patients. Immunohistochemistry revealed that 29 WHO grade I (45%), 10 WHO grade II (77%), and 4 WHO grade III (100%) tumors were VEGFR-2-positive, and that the VEGFR-2 expression was significantly correlated with the WHO grade. In univariate analyses to investigate the clinicopathological factors associated with recurrence, Simpson grade IV/V resection, a larger tumor size, a high VEGFR-2 expression level, WHO grade II/III, a high Ki-67 expression level, and the non-expression of PgR were identified as significant factors. Furthermore, patients with VEGFR-2-positive meningiomas showed significantly shorter progression-free survival. In the multivariate analysis, WHO grade II/III and the location were significantly associated with recurrence. In conclusion, our study suggests that VEGFR-2 inhibitors might be one of the best candidates for molecular therapy against recurrent meningiomas.

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References

  1. Perry A, Louis DN, Budka H, von Deimling A, Sahm F, Rushing EJ, Mawrin C, Claus EB, Loeffler J, Sadetzki S (2016) Meningiomas. WHO Classif. tumours Cent. Nerv. Syst. Revis, 4th edn, pp 232–245

  2. Kim D, Niemierko A, Hwang WL et al (2018) Histopathological prognostic factors of recurrence following definitive therapy for atypical and malignant meningiomas. J Neurosurg 128:1123–1132. https://doi.org/10.3171/2016.11.JNS16913

    Article  PubMed  Google Scholar 

  3. Ehresman JS, Garzon-Muvdi T, Rogers D et al (2018) The Relevance of Simpson grade resections in modern neurosurgical treatment of World Health Organization Grade I, II, and III meningiomas. World Neurosurg 109:e588–e593. https://doi.org/10.1016/j.wneu.2017.10.028

    Article  PubMed  Google Scholar 

  4. Karaman S, Leppänen V-M, Alitalo K (2018) Vascular endothelial growth factor signaling in development and disease. Development 145:dev151019. https://doi.org/10.1242/dev.151019

    Article  CAS  PubMed  Google Scholar 

  5. Tuchen M, Wilisch-Neumann A, Daniel EA et al (2017) Receptor tyrosine kinase inhibition by regorafenib/sorafenib inhibits growth and invasion of meningioma cells. Eur J Cancer 73:9–21. https://doi.org/10.1016/j.ejca.2016.12.004

    Article  CAS  PubMed  Google Scholar 

  6. Gupta S, Bi WL, Dunn IF (2018) Medical management of meningioma in the era of precision medicine. Neurosurg Focus 44:E3. https://doi.org/10.3171/2018.1.FOCUS17754

    Article  PubMed  Google Scholar 

  7. Allred DC, Harvey JM, Berardo M, Clark GM (1998) Prognostic and predictive factors in breast cancer by immunohistochemical analysis. Mod Pathol 11:155–168

    CAS  PubMed  Google Scholar 

  8. Kaneda Y (2013) Investigation of the freely available easy-to-use software ‘EZR’ for medical statistics. Bone Marrow Transplant 48:452–458. https://doi.org/10.1038/bmt.2012.244

    Article  Google Scholar 

  9. Barresi V, Lionti S, Caliri S, Caffo M (2018) Histopathological features to define atypical meningioma: what does really matter for prognosis? Brain Tumor Pathol 35:168–180. https://doi.org/10.1007/s10014-018-0318-z

    Article  PubMed  Google Scholar 

  10. Kampmann E, Altendorf-Hofmann A, Gibis S et al (2015) VEGFR2 predicts decreased patients survival in soft tissue sarcomas. Pathol Res Pract 211:726–730. https://doi.org/10.1016/j.prp.2015.04.015

    Article  CAS  PubMed  Google Scholar 

  11. Barresi V (2011) Angiogenesis in meningiomas. Brain Tumor Pathol 28:99–106. https://doi.org/10.1007/s10014-010-0012-2

    Article  CAS  PubMed  Google Scholar 

  12. Hilton DA, Shivane A, Kirk L et al (2016) Activation of multiple growth factor signalling pathways is frequent in meningiomas. Neuropathology 36:250–261. https://doi.org/10.1111/neup.12266

    Article  CAS  PubMed  Google Scholar 

  13. Kaley TJ, Wen P, Schiff D et al (2015) Phase II trial of sunitinib for recurrent and progressive atypical and anaplastic meningioma. Neuro Oncol 17:116–121. https://doi.org/10.1093/neuonc/nou148

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

The authors thank A. Nakayama for her technical assistance. This work was supported by Grant for Promoted Research from Kanazawa Medical University (S2018-8).

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Authors and Affiliations

  1. Department of Pathology and Laboratory Medicine, Kanazawa Medical University, 1-1 Daigaku, Uchinada, Ishikawa, 920-0293, Japan

    Satoko Nakada, Nozomu Kurose, Akihiro Shioya, Xin Guo, Sohsuke Yamada & Takayuki Nojima

  2. Department of Neurosurgery, Medical School, Kanazawa University, 13-1 Takaramachi, Kanazawa, Ishikawa, 920-8641, Japan

    Yasuo Sasagawa

  3. Department of Neurosurgery, Kanazawa Medical University, 1-1 Daigaku, Uchinada, Ishikawa, 920-0293, Japan

    Osamu Tachibana & Hideaki Iizuka

  4. Department of Orthopedic Surgery, Medical School, Kanazawa University, 13-1 Takaramachi, Kanazawa, Ishikawa, 920-8641, Japan

    Takayuki Nojima

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  1. Satoko Nakada
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  2. Yasuo Sasagawa
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  3. Osamu Tachibana
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  4. Hideaki Iizuka
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  7. Xin Guo
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  8. Sohsuke Yamada
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  9. Takayuki Nojima
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Correspondence to Satoko Nakada.

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Nakada, S., Sasagawa, Y., Tachibana, O. et al. The clinicopathological analysis of receptor tyrosine kinases in meningiomas: the expression of VEGFR-2 in meningioma was associated with a higher WHO grade and shorter progression-free survival. Brain Tumor Pathol 36, 7–13 (2019). https://doi.org/10.1007/s10014-018-0332-1

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  • DOI: https://doi.org/10.1007/s10014-018-0332-1

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