Expression of inhibitor-of-apoptosis protein (IAP) livin by neuroblastoma cells: correlation with prognostic factors and outcome.
Livin is a recently identified member of the Inhibitor-of-Apoptosis protein (IAP) family of antiapoptosis proteins, and expression has been reported in melanoma and some types of carcinoma. We evaluated livin expression in paraffin-embedded tumor tissue from 68 patients with neuroblastoma (NB) and 7 NB cell lines by immunoperoxidase using an anti-livin monoclonal antibody. Eighteen (26.5%) of the 68 NB tumor tissues showed high livin expression, 36 (53%) showed low-intermediate expression, and 14 (20.5%) were negative. Similarly, 4 NB cell lines showed high livin expression, and 3 showed intermediate expression. In primary NB tissue, livin was observed mainly in tumor neuropil, an extension of tumor cell cytoplasm, and the cytoplasm itself. By reverse transcriptase-polymerase chain reaction, livin expression was confirmed in all 7 NB lines and in frozen tissue from 1 of 3 primary tumors examined to date, in agreement with immunohistochemical data; both livin alpha and beta isoforms were detected. In the NB cases, we further analyzed the correlation between livin expression and clinical and biological features with established prognostic significance (i.e., age at diagnosis, stage, histology, and MYCN oncogene status), and patients' outcome. Livin expression alone did not appear to have an effect on survival; however, patients with high livin expression and amplified MYCN had significantly decreased survival compared with patients lacking both markers or with either of these markers alone. These results suggest that (a) livin is expressed in primary and cultured neuroblastoma cells and (b) high livin expression may identify a subset of neuroblastoma patients with a particularly poor prognosis among those with MYCN amplified tumors.
Kim
Dae-Kwang
DK
Department of Pediatrics, Emory University School of Medicine, Atlanta, GA 30322, USA.
Alvarado
Carlos S
CS
Abramowsky
Carlos R
CR
Gu
Lubing
L
Zhou
Muxiang
M
Soe
Minn-Minn
MM
Sullivan
Kevin
K
George
Bradley
B
Schemankewitz
Erwin
E
Findley
Harry W
HW
D048868:Adaptor Proteins, Signal Transducing / Q000096:biosynthesis*; D014408:Biomarkers, Tumor / Q000032:analysis*; D015139:Blotting, Southern; D045744:Cell Line, Tumor; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D051034:Inhibitor of Apoptosis Proteins / Q000096:biosynthesis*; D000071447:N-Myc Proto-Oncogene Protein; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D009367:Neoplasm Staging; D009447:Neuroblastoma / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D009687:Nuclear Proteins / Q000235:genetics; D015513:Oncogene Proteins / Q000235:genetics; D011379:Prognosis; D020033:Protein Isoforms / Q000096:biosynthesis; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016019:Survival Analysis; D015996:Survival Rate
D048868:Adaptor Proteins, Signal Transducing; C419866:BIRC7 protein, human; D014408:Biomarkers, Tumor; D051034:Inhibitor of Apoptosis Proteins; C459801:MYCN protein, human; D000071447:N-Myc Proto-Oncogene Protein; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D015513:Oncogene Proteins; D020033:Protein Isoforms; D012333:RNA, Messenger