Meningioma growth dynamics assessed by radiocarbon retrospective birth dating

Hagen B Huttner; Olaf Bergmann; Mehran Salehpour; Raouf El Cheikh; Makoto Nakamura; Angelo Tortora; Paula Heinke; Roland Coras; Elisabet Englund; Ilker Y Eyüpoglu; Joji B Kuramatsu; Sebastian S Roeder; Stephan P Kloska; Iris Muehlen; Arnd Doerfler; Stefan Schwab; Göran Possnert; Samuel Bernard; Jonas Frisén

doi:10.1016/j.ebiom.2017.12.020

Meningioma growth dynamics assessed by radiocarbon retrospective birth dating

EBioMedicine. 2018 Jan:27:176-181. doi: 10.1016/j.ebiom.2017.12.020. Epub 2017 Dec 19.

Authors

Hagen B Huttner¹, Olaf Bergmann², Mehran Salehpour³, Raouf El Cheikh⁴, Makoto Nakamura⁵, Angelo Tortora⁵, Paula Heinke⁶, Roland Coras⁷, Elisabet Englund⁸, Ilker Y Eyüpoglu⁹, Joji B Kuramatsu¹⁰, Sebastian S Roeder¹⁰, Stephan P Kloska¹¹, Iris Muehlen¹¹, Arnd Doerfler¹¹, Stefan Schwab¹⁰, Göran Possnert³, Samuel Bernard¹², Jonas Frisén¹³

Affiliations

¹ Department of Cell and Molecular Biology, Karolinska Institute, Sweden; Department of Neurology, University Hospital Erlangen, Germany.
² Department of Cell and Molecular Biology, Karolinska Institute, Sweden; DFG-Center for Regenerative Therapies Dresden, Technische Universität Dresden, Dresden, Germany.
³ Division of Ion Physics, Department of Physics and Astronomy, Uppsala University, Sweden.
⁴ Aix Marseille University, Inserm S 911 CRO2, SMARTc Pharmacokinetics Unit, Marseille, France.
⁵ Department of Neurosurgery, University Hospital Hannover, Germany.
⁶ DFG-Center for Regenerative Therapies Dresden, Technische Universität Dresden, Dresden, Germany.
⁷ Department of Neuropathology, University Hospital Erlangen, Germany.
⁸ Department of Pathology, University Hospital Lund, Sweden.
⁹ Department of Neurosurgery, University Hospital Erlangen, Germany.
¹⁰ Department of Neurology, University Hospital Erlangen, Germany.
¹¹ Department of Neuroradiology, University Hospital Erlangen, Germany.
¹² Institut Camille Jordan, CNRS UMR 5208, University of Lyon, Villeurbanne, France.
¹³ Department of Cell and Molecular Biology, Karolinska Institute, Sweden. Electronic address: [email protected].

Abstract

It is not known how long it takes from the initial neoplastic transformation of a cell to the detection of a tumor, which would be valuable for understanding tumor growth dynamics. Meningiomas show a broad histological, genetic and clinical spectrum, are usually benign and considered slowly growing. There is an intense debate regarding their age and growth pattern and when meningiomas should be resected. We have assessed the age and growth dynamics of 14 patients with meningiomas (WHO grade I: n=6 with meningothelial and n=6 with fibrous subtype, as well as n=2 atypical WHO grade II meningiomas) by combining retrospective birth-dating of cells by analyzing incorporation of nuclear-bomb-test-derived ¹⁴C, analysis of cell proliferation, cell density, MRI imaging and mathematical modeling. We provide an integrated model of the growth dynamics of benign meningiomas. The mean age of WHO grade I meningiomas was 22.1±6.5years, whereas atypical WHO grade II meningiomas originated 1.5±0.1years prior to surgery (p<0.01). We conclude that WHO grade I meningiomas are very slowly growing brain tumors, which are resected in average two decades after time of origination.

Keywords: C14; Meningioma; Radiocarbon; Tumor growth.

MeSH terms

Carbon Radioisotopes / chemistry*
Cell Proliferation
Cellular Senescence*
Humans
Meningioma / pathology*
Models, Biological
Radiopharmaceuticals / chemistry*

Substances

Carbon Radioisotopes
Radiopharmaceuticals