Originally published as JCO Early Release 10.1200/JCO.2005.00.562 on September 19 2005

This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Dome, J. S. Articles by Breslow, N. E. Search for Related Content PubMed PubMed Citation Articles by Dome, J. S. Articles by Breslow, N. E. Related Articles Related Editorial Social Bookmarking                            What's this?

High Telomerase RNA Expression Level Is an Adverse Prognostic Factor for Favorable-Histology Wilms' Tumor

From the Departments of Hematology/Oncology and Pathology, St Jude Children's Research Hospital, Memphis, TN; Department of Biostatistics, University of Washington, Seattle, WA; Department of Pediatrics, Roswell Park Cancer Institute, Buffalo, NY; and Department of Pathology, Children's Memorial Hospital, Chicago, IL

Address reprint requests to Jeffrey S. Dome, MD, Department of Hematology/Oncology, St Jude Children's Research Hospital, 332 N Lauderdale St, D5048C, Memphis, TN 38105; e-mail: jeff.dome{at}stjude.org

PURPOSE: 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.

PATIENTS AND 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.

CONCLUSION: Telomerase RNA expression level may provide a clinically useful adjunct to the current risk classification schema for favorable-histology Wilms' tumor.

Supported by Grant Nos. RO1 CA87903, P30 CA21765, and U10 CA42326 from the National Institutes of Health (Bethesda, MD) and by the American Lebanese Syrian Associated Charities of St Jude Children's Research Hospital.

Presented in part at the 40th Annual Meeting of the American Society of Clinical Oncology, New Orleans, LA, June 5-8, 2004.

Authors' disclosures of potential conflicts of interest are found at the end of this article.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

Related Editorial

• Standards for Reporting Prognostic Tumor Marker Studies
  Todd A. Alonzo
  JCO 2005 23: 9053-9054 [Full Text]

This article has been cited by other articles:

				Y. Stewenius, Y. Jin, I. Ora, J. de Kraker, J. Bras, A. Frigyesi, J. Alumets, B. Sandstedt, A. K. Meeker, and D. Gisselsson Defective Chromosome Segregation and Telomere Dysfunction in Aggressive Wilms' Tumors Clin. Cancer Res., November 15, 2007; 13(22): 6593 - 6602. [Abstract] [Full Text] [PDF]

				M. Kedde, C. le Sage, A. Duursma, E. Zlotorynski, B. van Leeuwen, W. Nijkamp, R. Beijersbergen, and R. Agami Telomerase-independent Regulation of ATR by Human Telomerase RNA J. Biol. Chem., December 29, 2006; 281(52): 40503 - 40514. [Abstract] [Full Text] [PDF]

				S. Trapp, M. S. Parcells, J. P. Kamil, D. Schumacher, B. K. Tischer, P. M. Kumar, V. K. Nair, and N. Osterrieder A virus-encoded telomerase RNA promotes malignant T cell lymphomagenesis J. Exp. Med., May 15, 2006; 203(5): 1307 - 1317. [Abstract] [Full Text] [PDF]

				T. A. Alonzo Standards for Reporting Prognostic Tumor Marker Studies J. Clin. Oncol., December 20, 2005; 23(36): 9053 - 9054. [Full Text] [PDF]