The survivin

Fas ratio is predictive of recurrent disease in neuroblastoma

Anthony Sandler, David Scott, Takeo Azuhata, Shigeru Takamizawa, Sue O'Dorisio

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Background/Purpose: Several clinical and biologic features of neuroblastoma (NB) are used to predict the risk of recurrent disease. The balance between antiapoptotic and proapoptotic factors within a tumor may affect its ability to survive. Survivin is an antiapoptotic factor expressed in highly proliferative NB, whereas Fas is a proapoptotic factor that portends a favorable prognosis. The authors determined whether the ratio of survivin to Fas (S:F ratio is predictive of recurrent disease in patients with NB. The authors previously have shown the S:F ratio is predictive of recurrent disease in pediatric renal tumors. Methods: The authors quantified the levels of 9 different apoptotic mRNA species using Rnase Protection assay (RPA, Riboquant, PharMingen, San Diego, CA). Twenty-eight primary tumor specimens were evaluated from patients with ganglioneuroma (n = 3), ganglioneuroblastoma (n = 2), and neuroblastoma (n = 23) from tumors of all clinical stages obtained at the time of diagnosis. mRNA levels were calculated as a percentage of L32 for each specimen assayed, and positive expression was assumed to be greater than 10% of L32. Results: Survivin was expressed in 90% of tumors that went on to recur and only in 27.7% of those that were cured. The S:F ratio was significantly greater in tumors that went on to recur (n = 10) compared with those from patients that were cured (n = 18) (median S:F ratio, 3.3 v 0.75; P = .0002, Wilcoxon rank-sum test). A cutoff ratio of 2.3 was highly predictive of tumor recurrence irrespective of clinical stage of disease (area under ROC curve = 0.906). Sensitivty was 80% (CI, 44.4% to 97.5%), specificty was 94.4% (CI, 72.7% to 99.9%), positive predictive value was 88.9% (CI, 51.8% to 99.7%), and negative predictive value was 89.5% (66.9% to 98.7%). Twenty-five of 28 (89.3%) tumor ratios were correct in predicting outcome. Conclusions: The survivin:Fas ratio in primary tumors may be used to predict the risk for recurrent disease in patients with NB. The S:F ratio appears to be a more sensitive predictor of recurrent disease than survivin expression alone. Determining this ratio may not only be helpful in guiding follow-up of patients with NB, but also may aid in stratifying patients for more aggressive therapeutic strategies.

Original languageEnglish (US)
Pages (from-to)507-511
Number of pages5
JournalJournal of Pediatric Surgery
Volume37
Issue number3
DOIs
StatePublished - 2002
Externally publishedYes

Fingerprint

Neuroblastoma
Neoplasms
Nonparametric Statistics
Ganglioneuroblastoma
Ganglioneuroma
Messenger RNA
Ribonucleases
ROC Curve
Area Under Curve
Pediatrics
Kidney
Recurrence

Keywords

  • Apoptosis
  • Fas
  • Neuroblastoma
  • Prognosis
  • Survivin

ASJC Scopus subject areas

  • Surgery

Cite this

The survivin : Fas ratio is predictive of recurrent disease in neuroblastoma. / Sandler, Anthony; Scott, David; Azuhata, Takeo; Takamizawa, Shigeru; O'Dorisio, Sue.

In: Journal of Pediatric Surgery, Vol. 37, No. 3, 2002, p. 507-511.

Research output: Contribution to journalArticle

Sandler, Anthony ; Scott, David ; Azuhata, Takeo ; Takamizawa, Shigeru ; O'Dorisio, Sue. / The survivin : Fas ratio is predictive of recurrent disease in neuroblastoma. In: Journal of Pediatric Surgery. 2002 ; Vol. 37, No. 3. pp. 507-511.
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abstract = "Background/Purpose: Several clinical and biologic features of neuroblastoma (NB) are used to predict the risk of recurrent disease. The balance between antiapoptotic and proapoptotic factors within a tumor may affect its ability to survive. Survivin is an antiapoptotic factor expressed in highly proliferative NB, whereas Fas is a proapoptotic factor that portends a favorable prognosis. The authors determined whether the ratio of survivin to Fas (S:F ratio is predictive of recurrent disease in patients with NB. The authors previously have shown the S:F ratio is predictive of recurrent disease in pediatric renal tumors. Methods: The authors quantified the levels of 9 different apoptotic mRNA species using Rnase Protection assay (RPA, Riboquant, PharMingen, San Diego, CA). Twenty-eight primary tumor specimens were evaluated from patients with ganglioneuroma (n = 3), ganglioneuroblastoma (n = 2), and neuroblastoma (n = 23) from tumors of all clinical stages obtained at the time of diagnosis. mRNA levels were calculated as a percentage of L32 for each specimen assayed, and positive expression was assumed to be greater than 10{\%} of L32. Results: Survivin was expressed in 90{\%} of tumors that went on to recur and only in 27.7{\%} of those that were cured. The S:F ratio was significantly greater in tumors that went on to recur (n = 10) compared with those from patients that were cured (n = 18) (median S:F ratio, 3.3 v 0.75; P = .0002, Wilcoxon rank-sum test). A cutoff ratio of 2.3 was highly predictive of tumor recurrence irrespective of clinical stage of disease (area under ROC curve = 0.906). Sensitivty was 80{\%} (CI, 44.4{\%} to 97.5{\%}), specificty was 94.4{\%} (CI, 72.7{\%} to 99.9{\%}), positive predictive value was 88.9{\%} (CI, 51.8{\%} to 99.7{\%}), and negative predictive value was 89.5{\%} (66.9{\%} to 98.7{\%}). Twenty-five of 28 (89.3{\%}) tumor ratios were correct in predicting outcome. Conclusions: The survivin:Fas ratio in primary tumors may be used to predict the risk for recurrent disease in patients with NB. The S:F ratio appears to be a more sensitive predictor of recurrent disease than survivin expression alone. Determining this ratio may not only be helpful in guiding follow-up of patients with NB, but also may aid in stratifying patients for more aggressive therapeutic strategies.",
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T2 - Fas ratio is predictive of recurrent disease in neuroblastoma

AU - Sandler, Anthony

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AU - Azuhata, Takeo

AU - Takamizawa, Shigeru

AU - O'Dorisio, Sue

PY - 2002

Y1 - 2002

N2 - Background/Purpose: Several clinical and biologic features of neuroblastoma (NB) are used to predict the risk of recurrent disease. The balance between antiapoptotic and proapoptotic factors within a tumor may affect its ability to survive. Survivin is an antiapoptotic factor expressed in highly proliferative NB, whereas Fas is a proapoptotic factor that portends a favorable prognosis. The authors determined whether the ratio of survivin to Fas (S:F ratio is predictive of recurrent disease in patients with NB. The authors previously have shown the S:F ratio is predictive of recurrent disease in pediatric renal tumors. Methods: The authors quantified the levels of 9 different apoptotic mRNA species using Rnase Protection assay (RPA, Riboquant, PharMingen, San Diego, CA). Twenty-eight primary tumor specimens were evaluated from patients with ganglioneuroma (n = 3), ganglioneuroblastoma (n = 2), and neuroblastoma (n = 23) from tumors of all clinical stages obtained at the time of diagnosis. mRNA levels were calculated as a percentage of L32 for each specimen assayed, and positive expression was assumed to be greater than 10% of L32. Results: Survivin was expressed in 90% of tumors that went on to recur and only in 27.7% of those that were cured. The S:F ratio was significantly greater in tumors that went on to recur (n = 10) compared with those from patients that were cured (n = 18) (median S:F ratio, 3.3 v 0.75; P = .0002, Wilcoxon rank-sum test). A cutoff ratio of 2.3 was highly predictive of tumor recurrence irrespective of clinical stage of disease (area under ROC curve = 0.906). Sensitivty was 80% (CI, 44.4% to 97.5%), specificty was 94.4% (CI, 72.7% to 99.9%), positive predictive value was 88.9% (CI, 51.8% to 99.7%), and negative predictive value was 89.5% (66.9% to 98.7%). Twenty-five of 28 (89.3%) tumor ratios were correct in predicting outcome. Conclusions: The survivin:Fas ratio in primary tumors may be used to predict the risk for recurrent disease in patients with NB. The S:F ratio appears to be a more sensitive predictor of recurrent disease than survivin expression alone. Determining this ratio may not only be helpful in guiding follow-up of patients with NB, but also may aid in stratifying patients for more aggressive therapeutic strategies.

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