The survivin:fas ratio in pediatric renal tumors

Shigeru Takamizawa, David Scott, Judy Wen, Paul Grundy, Warren Bishop, Ken Kimura, Anthony Sandler

Research output: Contribution to journalArticle

41 Scopus citations

Abstract

Background/Purpose: Apoptosis factors inducing or preventing cell death may govern the behavior of certain tumors. Fas is a pro-apoptotic receptor that induces cell death when bound by its ligand and is expressed at greater levels in pediatric renal tumors of good prognosis. Survivin is a novel inhibitor of apoptosis that is expressed in a cell cycle-dependent manner and is abundantly expressed in several tumors of unfavorable histology. This study evaluates the expression of survivin, as well as the prognostic value of the survivin:fas ratio in various types and stages of pediatric renal tumors. Methods: Multiple apoptosis mRNA species were quantified by Rnase protection assay (RPA) in 32 pediatric renal tumors and adjacent normal kidney specimens before chemotherapy: Wilms' tumor (WT), n = 9; clear cell sarcoma (CCS), 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 survey. Follow-up data were obtained on patient outcomes, and antiapoptotic to proapoptotic ratios were calculated and correlated with clinical recurrence of disease. Results: Pediatric renal tumors express greater levels of both pro- and antiapoptotic factors than normal kidney. Survivin and fas appeared to be expressed differentially in the tumor specimens sampled. Five of 10 (50%) tumors 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%) tumors that recurred were fas positive, whereas 5 of 11 (45%) tumors that did not recur expressed fas. The mean survivin:fas ratio was significantly greater 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 v 1.0 ± 1.07; P = .01, Kruskal-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% (CI: 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 ability to predict recurrent disease in children undergoing treatment for pediatric renal tumors. In this series, a ratio of greater than 1.6 predicted recurrent disease with a high probability irrespective of clinical stage or pathologic type. Determining the survivin:fas ratio may guide treatment, follow-up and counseling of patients with pediatric renal tumors.

Original languageEnglish (US)
Pages (from-to)37-42
Number of pages6
JournalJournal of pediatric surgery
Volume36
Issue number1
DOIs
StatePublished - Jan 1 2001
Externally publishedYes

Keywords

  • Apoptosis factors
  • Fas
  • Pediatric renal tumors
  • Prognosis
  • Survivin

ASJC Scopus subject areas

  • Surgery
  • Pediatrics, Perinatology, and Child Health

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  • Cite this

    Takamizawa, S., Scott, D., Wen, J., Grundy, P., Bishop, W., Kimura, K., & Sandler, A. (2001). The survivin:fas ratio in pediatric renal tumors. Journal of pediatric surgery, 36(1), 37-42. https://doi.org/10.1053/jpsu.2001.20000