High telomerase reverse transcriptase (hTERT) messenger RNA level correlates with tumor recurrence in patients with favorable histology Wilms' tumor

Telomerase is a reverse transcriptase that maintains chromosome ends, compe nsating for the progressive loss of DNA that occurs during replication. Hig h telomerase enzyme activity is an unfavorable prognostic feature for sever al types of cancers, We investigated whether telomerase level predicts outc ome for patients with the pediatric renal malignancy Wilms' tumor. In a cas e-cohort study of 78 patients with favorable histology Wilms' tumor, we com pared tumor telomerase levels in patients with and without eventual recurre nce. Three measures of telomerase were used: (a) telomerase enzyme activity ; (b) expression of hTR, the RNA component of telomerase; and (c) mRNA expr ession of hTERT, the gene that encodes the catalytic component of the enzym e, Of the evaluable samples, 81% had detectable telomerase activity, 97% ha d detectable hTERT transcript, and 100% had detectable hTR, Weak correlatio ns were observed between telomerase activity and hTR level (r = 0.34, P = 0 .02) and between telomerase activity and hTERT mRNA level (r = 0.32, P = 0. 04). Of the variables assessed, only hTERT mRNA expression correlated with outcome. The median hTERT mRNA level in tumors with recurrence was higher t han that in tumors without recurrence (1.42 versus 0.97 units, P = 0.023, W ilcoxon), Univariate analysis of hTERT mRNA level as a continuous variable suggested that each unit increase in hTERT mRNA level increased the risk of recurrence (RR) by a factor of 1.66 [95% confidence interval (CI), 1.2-2.3 ; P < 0.005]. Compared with tumors with hTERT mRNA levels of 0-1 units, tum ors with hTERT mRNA levels of 1-2 units had a RR of 2.72 (95% CI, 0.91-8.13 ; P = 0.074), and tumors with hTERT mRNA levels > 2 units had a RR of 6.40 (95% CI, 1.49-27.67, P = 0.013). Multivariate analysis of hTERT mRNA level as a predictor of recurrence, adjusted for tumor stage and age at diagnosis , revealed a RR of 1.48 (95% CI, 0.9-2.6; P = 0.16), Measurement of hTERT m RNA level may, therefore, enable clinicians to identify a population of pat ients at high risk for recurrence and to adjust their therapy accordingly. A larger study will be necessary to determine whether hTERT expression is a n independent prognostic Indicator, Further biological investigation is war ranted to discern whether the link between high hTERT expression and unfavo rable prognosis is causative or correlative.