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 with 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 was significantly associated with survival in neuroblastomas (P<0.049) and in PNET/medulloblastomas (P=0.01). Expression of Apo-3 was significantly associated with survival in PNET/medulloblastomas (P=0.03). Thus, the Apo-3 receptor/ligand system might be involved in the regulation of apoptosis in neuroblastomas and PNET.
Eggert
A
A
Division of Oncology and Biostatistics, The Children's Hospital of Philadelphia, PA 19104, USA.
Grotzer
M A
MA
Zuzak
T J
TJ
Ikegaki
N
N
Zhao
H
H
Brodeur
G M
GM
D000293:Adolescent; D016543:Central Nervous System Neoplasms / Q000378:metabolism*; D002528:Cerebellar Neoplasms / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008024:Ligands; D008527:Medulloblastoma / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000378:metabolism*; D009447:Neuroblastoma / Q000378:metabolism*; D010524:Peripheral Nervous System Neoplasms / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D012334:RNA, Neoplasm / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism*; D053219:Receptors, Tumor Necrosis Factor, Member 25; D012044:Regression Analysis; D016019:Survival Analysis; D014407:Tumor Cells, Cultured
D008024:Ligands; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D018124:Receptors, Tumor Necrosis Factor; D053219:Receptors, Tumor Necrosis Factor, Member 25; C506033:TNFRSF25 protein, human