Expression of Apo-3 and Apo-3L in primitive neuroectodermal tumours of the central and peripheral nervous system

Deregulation of apoptosis has been implicated in the pathogenesis, spontaneous regression and treatment resistance of neuroblastoma. A newly recognised member of the tumour necrosis factor (TNF)-family of death receptors known as Apo-3 has been mapped to human chromosome 1p36.3 a region commonly deleted in aggressive neuroblastoma. Based on its localisation and function, Apo-3 is a candidate for the putative neuroblastoma tumour suppressor gene. Therefore we analysed mRNA expression of the Apo-3 receptor ligand (Apo-3 Apo-3L) system in a representative panel of 18 neuroblastoma cell lines. 41 primary neuroblastoma and 13 ganglioneuromas, ganglioneuroblastomas by semi-quantitative RT-PCR. We compared the level of expression with the well-established prognostic factors age, stage, histology, MYCN-amplification and TrkA expression, as well as outcome. For comparison, we studied Apo-3, Apo-3L expression in 27 central nervous system (CNS) primitive neuroectodermal tumours medulloblastomas (PNET,medulloblastoma) and in six normal brain samples. Neuroblastoma cell lines 1p deletion and MYCN-amplification expressed significantly lower levels of Apo-3 (P=0.009 and P=0.03. respectively) compared with neuroblastoma cell lines without 1p deletion or MYCN-amplification. The mean expression level of Apo-3L was significantly higher in ganglioneuromas, ganglioneuroblastomas compared with neuroblastomas (P-0.001) and in normal brain compared with PNET medulloblastoma (P<0.0001). Expression of Apo-3L significantly associated with survival in neuroblastomas (P<0.049) and in PNET,medulloblastomas (P=0.01). Expression of Apo-3L as significantly associated with in PNET medulloblastoma (P=0.03). Thus, the Apo-3 receptor ligand system might be invoked in the regulation of apoptosis in neuroblastomas and PNET. (C) 2002 Published by Elsevier Science Ltd.