TSPO expression in human gliomas

Expression of the mitochondrial 18 kda translocator protein in Human astrocytomas and oligodendrogliomas and its association With endogenous cortisol synthesis

Karolina Janczar 1, Jonathan E Bowen 2, Nelofer Syed 1, Manuel Deprez 3, Emilie Croisier 1, Sally Davidson-Von Holt 4, Amanda Forsyth 5, Kevin O’Neill 1, James Van Dellen 1, Atsushi Sasaki 6, Federico E Turkheimer 1, Federico Roncaroli 1

1: Department of Clinical Neuroscience & “John Fulcher” BTRC Brain Tumor Research Group, Division of Neuroscience and Mental Health, Imperial College, London, UK
2: Department of Biomolecular Medicine, Division of Surgery, Oncology, Reproductive Biology and Anaesthetics, Imperial College, London UK
3: Laboratory of Neuropathology, Department of Pathology, University Hospital of Liège, Belgium
4: ECMC and BTRC Brain Tumor Registry, Imperial College London
5: Human Biomaterials Resource Centre, Imperial College, London, UK
6: Department of Human Pathology, University Graduate School of Medicine, Gunma University, Japan

ABSTRACT
Purpose of this study is to investigate the expression of the mitochondrial 18 kDa translocator protein (TSPO) in human astrocytomas and oligodendrogliomas and assess its possible association with cortisol synthesis. We used immunohistochemistry and western blotting to detect TSPO, the key corticosteroidogenic enzymes P450scc, P450c17α1 and P450c11β1, cortisol and phosphorylated glucocorticoid receptor in 50 supratentorial gliomas (30 astrocytomas and 20 oligodendrogliomas) from adults who underwent surgical debulking. All lesions showed TSPO in neoplastic cells and its expression was associated with the presence of corticosteroidogenic enzymes and cortisol. TSPO expression was significantly higher in astrocytomas (average 50.6%, median 47.1%) than oligodendrogliomas (average 9.9%, median 4.5%). In all cases, TSPO-positive microglial cells accounted for a minority of tumor infiltrating microglia identified with Iba1 and only a few showed the expression of corticosteroidogenic enzymes. Thirty-eight tumors showed phosphorylated glucocorticoid receptor in neoplastic cells and to much lesser extent, microglia. The evidence of an association between TSPO and endogenous cortisol synthesis in gliomas is novel and sheds light on the role of TSPO in these tumors. Our results may provide new insights into their metabolism and the immunosuppressive properties of their microenvironment and explain the different natural history and chemosensitivity between astrocytomas and oligodendrogliomas.