High telomerase RNA expression level is an adverse prognostic factor for favorable-histology Wilms' tumor.
OBJECTIVE
A primary objective of the fifth National Wilms Tumor Study (NWTS-5) was to identify prognostic indicators for patients with favorable-histology Wilms' tumor. The prognostic significance of telomerase expression level in primary tumor samples was assessed.


METHODS
A case-cohort study was conducted involving 291 NWTS-5 registrants. Telomerase activity was measured using the telomeric repeat amplification protocol (TRAP). Expression levels of TERT mRNA (encoding the telomerase catalytic component) and TERC/hTR (the telomerase RNA template) were measured using quantitative real-time polymerase chain reaction.


RESULTS
After excluding samples because of lack of viable tumor, RNA degradation, or insufficient clinical information, 244 patients remained for the final analysis (96 with relapse and 148 without relapse). Univariate analysis revealed a positive correlation between relative risk (RR) of relapse and levels of TERT mRNA and TERC expression. For each doubling in TERT mRNA and TERC level, the RR increased by a factor of 1.16 (95% CI, 1.04 to 1.29; P = .01) and 1.35 (95% CI, 1.11 to 1.64; P = .003), respectively. The one third of patients whose tumors had the highest TERC expression level had an RR of 2.06 (95% CI, 1.14 to 3.70; P = .02) compared with patients with the lowest level. TERC expression level remained a significant prognostic indicator in a multivariate analysis adjusting for TERT mRNA, tumor stage, and patient age. TRAP level did not correlate with RR of relapse. Telomerase expression levels were not predictive of overall survival.


CONCLUSIONS
Telomerase RNA expression level may provide a clinically useful adjunct to the current risk classification schema for favorable-histology Wilms' tumor.
Dome
Jeffrey S
JS
Department of Hematology/Oncology, St Jude Children's Research Hospital, Memphis, TN 38105, USA. jeff.dome@stjude.org
Bockhold
Carol A
CA
Li
Sierra M
SM
Baker
Scott D
SD
Green
Daniel M
DM
Perlman
Elizabeth J
EJ
Hill
D Ashley
DA
Breslow
Norman E
NE
D014408:Biomarkers, Tumor / Q000032:analysis; D016022:Case-Control Studies; D002675:Child, Preschool; D015331:Cohort Studies; D004268:DNA-Binding Proteins / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007680:Kidney Neoplasms; D008297:Male; D015999:Multivariate Analysis; D016133:Polymerase Chain Reaction; D011379:Prognosis; D012313:RNA / Q000096:biosynthesis; D012307:Risk Factors; D019098:Telomerase / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics; D009396:Wilms Tumor
D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D012313:RNA; C509186:TERT protein, human; D019098:Telomerase