HDM2 overexpression and focal loss of p14/ARF expression may deregulate the p53 tumour suppressor pathway in meningeal haemangiopericytomas. Study by double immunofluorescence and laser scanning confocal microscopy
J-C Martínez,
J-C Palomino,
A Cabello,
J M Sepúlveda, A G De La Cámara,
J-R Ricoy,
J-C Martínez
Department of Pathology (Neuropathology), Services of Neurosurgery
Search for more papers by this authorJ-C Palomino
Department of Pathology (Neuropathology), Services of Neurosurgery
Search for more papers by this authorA Cabello
Department of Pathology (Neuropathology), Services of Neurosurgery
Search for more papers by this authorA G De La Cámara
Research and Epidemiology Unit, University Hospital ‘12 de Octubre’, Madrid, Spain
Search for more papers by this authorJ-R Ricoy
Department of Pathology (Neuropathology), Services of Neurosurgery
Search for more papers by this authorJ-C Martínez,
J-C Palomino,
A Cabello,
J M Sepúlveda, A G De La Cámara,
J-R Ricoy,
J-C Martínez
Department of Pathology (Neuropathology), Services of Neurosurgery
Search for more papers by this authorJ-C Palomino
Department of Pathology (Neuropathology), Services of Neurosurgery
Search for more papers by this authorA Cabello
Department of Pathology (Neuropathology), Services of Neurosurgery
Search for more papers by this authorA G De La Cámara
Research and Epidemiology Unit, University Hospital ‘12 de Octubre’, Madrid, Spain
Search for more papers by this authorJ-R Ricoy
Department of Pathology (Neuropathology), Services of Neurosurgery
Search for more papers by this authorDr J R Ricoy MD, PhD, Department de Anatomía Patológica (Neuropatología), Hospital Universitario ‘12 de Octubre, Avda de Córdoba s/n, 28041 Madrid, Spain. e-mail:[email protected]
Abstract
Aims : To investigate the p53 pathway in meningeal haemangiopericytomas (MHPCs), p14/ARF, p53 protein expression and two wild-type (wt) p53-induced proteins (HDM2 and p21/WAF1) were studied in 18 MHPCs, 11 primary, four of them recurrent on one, one, two and four occasions.
Methods : Immunohistochemical detection of p14/ARF, p53, p21/WAF1, HDM2 and Ki67 proliferative index (PI) protein expression.
Results : Ki67 index was > 5% in eight out 18 cases (44.4%). The PI in recurrent cases increased with neoplastic progression. Simultaneous p53 and wt p53 transactivated gene (p21/WAF, HDM2) expression occurred in all cases. This argues against p53 mutation. HDM2 overexpression was observed in 10 cases (55.5%). Double-immunofluorescence staining and laser scanning confocal microscopy (LSCM) displayed HDM2 and p53 colocalization. This strongly suggests that HDM2 binds and inactivates p53 that could be pathogenic for MHPCs, by a different mechanism than point mutation. p14/ARF expression > 5% was observed in 12 cases (66.6%). A normal (diffuse) pattern of expression was seen in 13 cases (72.2%). Focal loss of expression was observed in five patients (27.7%): three primary cases and two recurrences. Therefore, p14/ARF down-regulation may also contribute to the development of MHPC.
Conclusion : HDM2 overexpression, sometimes combined with focal loss of p14/ARF expression, may play a pathogenic role in MHPCs.
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