The Survivin : Fas ratio in pediatric renal tumors

Background/Purpose: Apoptosis factors inducing or preventing cell death may govern the behavior of certain tumors. Fas is a pro-apoptotic receptor tha t induces cell death when bound by its ligand and is expressed at greater l evels in pediatric renal tumors of good prognosis. Survivin is a novel inhi bitor of apoptosis that is expressed in a cell cycle-dependent manner and i s abundantly expressed in several tumors of unfavorable histology. This stu dy evaluates the expression of survivin, as well as the prognostic value of the survivin:fas ratio in various types and stages of pediatric renal tumo rs. Methods: Multiple apoptosis mRNA species were quantified by Rnase protectio n assay (RPA) in 32 pediatric renal tumors and adjacent normal kidney speci mens before chemotherapy: Wilms' tumor (:WT), n = 9; clear cell sarcoma (CC S), n = 4; rhabdoid tumor of the kidney (RTK), n = 5; mesoblastic nephroma (MN), n = 3 and normal kidney, n = 11. Western Blot and immunocytochemistry were used to confirm survivin protein expression in a selective specimen s urvey. Follow-up data were obtained on patient outcomes, and antiapoptotic to proapoptotic ratios were calculated and correlated with clinical recurre nce of disease. Results: Pediatric renal tumors express greater levels of both pro- and ant iapoptotic factors than normal kidney. Survivin and fas appeared to be expr essed differentially in the tumor specimens sampled. Five of 10 (50%) tumor s that went on to recur expressed survivin, whereas survivin was present in only 2 of 11 (18%) nonrecurrent tumors. Conversely, only 2 of 10 (20%) tum ors that recurred were fas positive, whereas 5 of 11 (45%) tumors that did not recur expressed fas. The mean survivin:fas ratio was significantly grea ter in the 10 tumors that went on to recur after treatment (4 RTK, 3 CCS, 3 WT), than in tumors not recurring (2.16 +/- 1.4 v1.0 +/- 1.07; P =.01, Kru skal-Wallis test). The positive predictive value of tumor recurrence was 85 .7% (CI: 42.1%, 99.6%) and the negative predictive value was 71.4% ICI: 41. 9%, 91.6%) when a cutoff ratio of 1.6 was considered. Conclusions: The survivin:fas mRNA ratio is of prognostic value in its abil ity to predict recurrent disease in children undergoing treatment for pedia tric renal tumors. In this series, a ratio of greater than 1.6 predicted re current disease with a high probability irrespective of clinical stage or p athologic Type. Determining the survivin:fas ratio may guide treatment, fol low-up and counseling of patients with pediatric renal tumors. J Pediatr Su rg 36:37-42. Copyright (C) 2001 by W.B. Saunders Company.