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

39 Citations (Scopus)

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 - 2001
Externally publishedYes

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Pediatrics
Kidney
Neoplasms
Clear Cell Sarcoma
Rhabdoid Tumor
Cell Death
Mesoblastic Nephroma
Apoptosis Inducing Factor
Apoptosis
Recurrence
Messenger RNA
Aptitude
Wilms Tumor
Ribonucleases
Counseling
Histology
Cell Cycle
Therapeutics
Western Blotting
Immunohistochemistry

Keywords

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

ASJC Scopus subject areas

  • Surgery

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

The survivin : fas ratio in pediatric renal tumors. / Takamizawa, Shigeru; Scott, David; Wen, Judy; Grundy, Paul; Bishop, Warren; Kimura, Ken; Sandler, Anthony.

In: Journal of Pediatric Surgery, Vol. 36, No. 1, 2001, p. 37-42.

Research output: Contribution to journalArticle

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, vol. 36, no. 1, pp. 37-42. https://doi.org/10.1053/jpsu.2001.20000
Takamizawa, Shigeru ; Scott, David ; Wen, Judy ; Grundy, Paul ; Bishop, Warren ; Kimura, Ken ; Sandler, Anthony. / The survivin : fas ratio in pediatric renal tumors. In: Journal of Pediatric Surgery. 2001 ; Vol. 36, No. 1. pp. 37-42.
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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.",
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KW - Prognosis

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