Prognostic value of quantifying apoptosis factor expression in favorable histology wilms tumors.
Important in the homeostasis of normal tissues, apoptosis can be altered to favor cell survival within tumors. High expression of survivin, an inhibitor of apoptosis, and absence of caspase 8, a pro-apoptotic enzyme, independently correlate with poor outcomes in several tumor types. Favorable histology Wilms tumor has a remarkably high cure rate; as a result, the focus of therapy is now aimed at reducing treatment-related morbidity. With the goal of safely reducing therapy in select subgroups of patients, the authors investigated whether the levels of apoptotic factors in tumors could predict the risk for recurrence. Tumor apoptotic factor levels were surveyed in a case-control study from the National Wilms Tumor Study 5 (NWTS-5) and measured via quantitative real-time RT-PCR. Survivin and caspase 8 levels were surveyed in 92 primary tumor specimens and SMAC, Bid, and CD95 were surveyed in 24 specimens. All four pro-apoptotic factors studied (caspase 8, SMAC, Bid, and CD95) were analyzed individually and in relation to survivin expression. Although survivin mRNA was present at markedly greater levels than in normal kidney, none of the factors assayed independently or as a ratio was associated with stage of disease or risk for tumor recurrence in this group of tumors.
Miller
Michal A
MA
Department of Surgery, University of Iowa, Iowa City, Iowa 52242, USA.
Karacay
Bahri
B
Breslow
Norman E
NE
Li
Sierra
S
O'Dorisio
M Sue
MS
Grundy
Paul E
PE
Sandler
Anthony D
AD
D017209:Apoptosis / Q000502:physiology*; D051023:BH3 Interacting Domain Death Agonist Protein; D014408:Biomarkers, Tumor / Q000032:analysis*; D002352:Carrier Proteins / Q000378:metabolism; D016022:Case-Control Studies; D053181:Caspase 8; D020169:Caspases / Q000378:metabolism; D015870:Gene Expression; D051034:Inhibitor of Apoptosis Proteins; D007680:Kidney Neoplasms / Q000378:metabolism* / Q000473:pathology; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000378:metabolism; D009363:Neoplasm Proteins; D011379:Prognosis; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000077022:Survivin; D009396:Wilms Tumor / Q000378:metabolism* / Q000473:pathology; D019014:fas Receptor / Q000378:metabolism
D051023:BH3 Interacting Domain Death Agonist Protein; C107489:BIRC5 protein, human; D014408:Biomarkers, Tumor; D002352:Carrier Proteins; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D024101:Mitochondrial Proteins; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D000077022:Survivin; D019014:fas Receptor; C505530:CASP8 protein, human; D053181:Caspase 8; D020169:Caspases