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Prognostic significance of VEGF receptors expression on the tumor cells in skull base chordoma

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Abstract

Background

Chordoma is a rare refractory neoplasm that arises from the embryological remnants of the notochord, which is incurable using any multimodality therapy. Vascular endothelial growth factor (VEGF) is a potent activator of angiogenesis that is strongly associated with the tumor-immune microenvironment. These factors have not been elucidated for chordomas.

Methods

To evaluate the characteristics of vascular and tumor cells in chordoma, we first analyzed the expression of VEGF receptor (VEGFR) 1, VEGFR2, CD34, and Brachyury in a cell line and 54 tumor tissues. Patients with primary skull base chordomas were divided into the following two groups as per the tumor growth rate: patients with slow progression (SP: < 3 mm/year) and those with rapid progression (RP: ≥ 3 mm/year). Thus, the expressions of VEGF-A, VEGFR 1, and VEGFR2 on tumor cells; tumor infiltrative immune cells, including regulatory T cells (Tregs) and tumor-associated macrophages (TAMs); and immune-checkpoint molecules (PD-1/PD-L1) were analyzed with the clinical courses, especially in a comparison between the two groups.

Results

In chordomas, both VEGFR1 and VEGFR2 were strongly expressed not only on vascular endothelial cells, but also on tumor cells. The recurrent cases showed significantly higher VEGFR1 expressions on tumor cells than the primary cases. The expression of VEGF-A was significantly higher in RP than that in SP group. The numbers of CD163+ TAMs and Foxp3+ Tregs were higher in RP than that in SP group.

Conclusions

Expression of VEGFR1 and VEGFR2 on tumor cells and immunosuppressive tumor-microenvironment were related to tumor growth in patients with chordomas.

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Acknowledgements

The authors greatly thank Ms. Naoko Tsuzaki in the department of Neurosurgery for technical assistance of laboratory works.

Funding

This work was supported in part by grants from the Japan Society for the Promotion of Science (JSPS) (17H04306 to M.T.).

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Authors and Affiliations

  1. Department of Neurosurgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan

    Yukina Morimoto, Ryota Tamura, Kenzo Kosugi, Yumiko Oishi, Yuki Kuranari, Kazunari Yoshida & Masahiro Toda

  2. Department of Pathology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan

    Kentaro Ohara

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  1. Yukina Morimoto
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Correspondence to Masahiro Toda.

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Morimoto, Y., Tamura, R., Ohara, K. et al. Prognostic significance of VEGF receptors expression on the tumor cells in skull base chordoma. J Neurooncol 144, 65–77 (2019). https://doi.org/10.1007/s11060-019-03221-z

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