Prognostic impact of telomerase activity in patients with neuroblastoma.

Abstract

Neuroblastoma is one of the most common malignant neoplasms occurring among children. The prognosis for this disease is strongly associated with age, disease stage, histology, and some biologic features. It has been reported that telomerase, a ribonucleoprotein enzyme, which maintains the telomere length in immortal cells, is related to disease stage and other biologic features. The purpose of this study was to evaluate the prognostic value of telomerase activity compared to TrkA expression in 65 patients with neuroblastoma. Telomerase activity and TrkA expression were examined in tissue samples collected between 1980 and 1994 from 65 patients by polymerase chain reaction-based telomerase activity. TrkA expression was examined by immunoblotting using a rabbit anti-gp140 proto-trk polyclonal antibody. Low telomerase activity was found in 22 of 30 (73.3%) patients with Stages 1, 2, or 4S neuroblastomas; 7 of 13 (53.8%) with Stage 3; and 8 of 22 (36.3%) with stage 4; no telomerase activity was detected in 7 of 22 (31.8%) patients with Stage 4 neuroblastoma. The 5-year event-free survival (EFS) rate was 86.5% for patients with low telomerase activity, while it was 53.8% for patients with high telomerase activity. By the combination of telomerase activity and TrkA expression, the 5-year EFS rate was highest among patients with a high TrkA expression and a low or non-existent telomerase activity (91.7%), and it was lowest among patients with a low TrkA expression and a high telomerase activity (29.6%). Thus, it appears that telomerase activity would be a useful prognostic factor for neuroblastoma, especially when used in combination with the TrkA expression.