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.
|
Authors | S Takamizawa, D Scott, J Wen, P Grundy, W Bishop, K Kimura, A Sandler |
Journal | Journal of pediatric surgery
(J Pediatr Surg)
Vol. 36
Issue 1
Pg. 37-42
(Jan 2001)
ISSN: 0022-3468 [Print] United States |
PMID | 11150435
(Publication Type: Journal Article)
|
Chemical References |
- BIRC5 protein, human
- Inhibitor of Apoptosis Proteins
- Microtubule-Associated Proteins
- Neoplasm Proteins
- Proteins
- RNA, Messenger
- Survivin
- fas Receptor
|
Topics |
- Apoptosis
- Blotting, Western
- Child
- Humans
- Immunoenzyme Techniques
- Inhibitor of Apoptosis Proteins
- Kidney Neoplasms
(metabolism)
- Microtubule-Associated Proteins
- Neoplasm Proteins
- Neoplasm Recurrence, Local
(diagnosis)
- Predictive Value of Tests
- Prognosis
- Proteins
(metabolism)
- RNA, Messenger
(metabolism)
- Statistics, Nonparametric
- Survivin
- fas Receptor
(metabolism)
|