TPPP/p25 in brain tumours: expression in non-neoplastic oligodendrocytes but not in oligodendroglioma cells

Abstract

In normal rat and human brain tubulin, polymerization-promoting protein TPPP/p25 is predominantly localized in oligodendrocytes (Kovacs et al. in Neurobiol Dis 17:155–162, 2004; Lindersson et al. in J Biol Chem 280:5703–5715, 2005; Skjoerringe et al. in J Neurochem 99:333–342, 2006). TPPP/p25 promotes the polymerization of tubulin into double walled tubules and polymorphic aggregates and inhibits mitotic spindle assembly in vitro; furthermore, it is a common marker of -synuclein bearing pathological inclusions (summarized in detail: Kovacs et al., Acta Neuropath, this issue). Oligodendroglioma, oligoastrocytoma, clear cell ependymoma, and central neurocytoma share a common feature: the clear cell histopathology (Kleihues and Cavenee, IARC Press, Lyon, 2000). Therefore, diVerential diagnosis of clear cell primary brain tumours in the diagnostic setting often requires immunohistochemistry (Koperek et al. in Acta Neuropathol 108:24–30, 2004; Preusser et al. in Histopathology, in press). In this study, we evaluated the reliability of TPPP/p25 as an immunohistochemical marker of oligodendroglial neoplasms in the classiWcation and neuropathological diagnosis of primary clear cell brain tumours. Our cohort of human clear cell CNS neoplasms comprised 57 oligodendroglial neoplasms with chromosome 1p aberrations (1p deletion or imbalance status in 20 oligodendrogliomas, 20 anaplastic oligodendrogliomas, 17 oligoastrocytomas; 51/57 of these tumours additionally had aberrations of chromosome 19q), 3 oligodendroglial neoplasms without chromosome 1p aberration (2 oligodendrogliomas, 1 oligoastrocytoma), 10 central neurocytomas, 10 clear cell ependymomas, and 8 dysembryoplastic neuroepithelial tumours (DNTs). Further, we investigated 20 diVuse astrocytomas and glioblastomas, as well as 5 glioblastomas with clear cell components. Tumour typing was performed according to WHO criteria (Kleihues and Cavenee, IARC Press, Lyon, 2000). Aberrations of chromosome 1p and 19q were assessed by Xuorescence in situ hybridization (FISH) using the paracentromeric probe D1Z1 (1q12) and the subtelomeric probe D1Z2 (1p36.3; both Q-BIOgene, Heidelberg, Germany) for 1p and probes 19pter and 19q13.3 (both Vysis, BergishGladbach, Germany) for 19q as described in a previous study by our group (Gelpi et al. in Mod Pathol 16:708– 715, 2003). We also immunostained ten biopsy samples of non-neoplastic temporal cortex from patients diagnosed with chronic temporal lobe epilepsy. For immunohistochemistry, tissue specimens were Wxed in a phosphate-buVered 4.5% solution of formaldehyde, embedded in paraYn and cut at a thickness of 3–5 m. Sections were deparaVinized in xylene. Slides underwent heat induced epitope retrieval in 0.01 M citrate buVer (pH 6.0) in a steamer for 10 min. For antiTPPP/p25 immunostaining, we used two rat polyclonal M. Preusser · H. Budka · G. G. Kovacs Institute of Neurology, Medical University of Vienna, Vienna, Austria