Quantitative telomerase expression in glioblastomas shows regional variation and down-regulation with therapy but no correlation with patient outcome

Despite the nearly ubiquitous expression of telomerase in almost all types of malignant human tumors, studies have shown widely varying positivity in the highest-grade glioma, the glioblastomas (GBMs), ranging from 26% to 100 % of tumors analyzed. We have previously shown significant variability in p ositive versus negative telomerase expression from region to region within the same GEM. In this study, we hypothesized that application of new quanti tative methodology would extend our previous observations and identify whet her there is heterogeneity in levels of protein expression even within area s positive for telomerase in high-grade gliomas. Finally, we sought to corr elate quantitative telomerase expression with patient outcome and therapeut ic response. Quantitative analysis was achieved by polymerase chain-based T RAP assay with phosphorimager analysis and compared with clinical informati on obtained from 19 patients, most with primary, untreated GBMs. Results sh owed up to 3-fold variability in telomerase levels across multiple regional samples from the same patient, as well. as between patients. In 5 of 6 pat ients with recurrent tumors who had received intervening radiation therapy or chemotherapy, telomerase was downregulated in the second, post-therapy s ample. These data provide in vivo corroboration of recent in vitro experime nts showing telomerase downregulation after radiation therapy or chemothera py treatment of cell lines. Our finding of variability in levels of telomer ase expression in GBMs parallels the known heterogeneity of these tumors fo r histologic features and cell growth-related factors. Statistical analysis showed no relationship between TRAP score and either time to clinical prog ression or time to death. Copyright (C) 2000 by W.B. Saunders Company.