TELOMERASE EXPRESSION SHOWS DIFFERENCES ACROSS MULTIPLE REGIONS OF OLIGODENDROGLIOMA VERSUS HIGH-GRADE ASTROCYTOMAS BUT SHOWS CORRELATION WITH MIB-1 LABELING

Aims/Background-Telomerase is an enzyme that is expressed in most huma n neoplasms and is associated with tumour immortality. Determination o f the point in neoplastic transformation at which telomerase is expres sed may aid the understanding of tumour pathogenesis and progression. Despite numerous reports on telomerase, few studies have investigated its expression in high grade glial tumours. These studies, performed o n archival banked, single brain tumour specimens, have shown conflicti ng results for oligodendrogliomas and unexpectedly negative results fo r telomerase expression in high grade astrocytomas, with one third to one half of glioblastoma multiformes being negative. Methods-34 rapidl y banked glioma specimens taken from patients undergoing gross total s urgical resection of their tumours were studied. Telomerase expression was assessed across 3-8 sampled regions from each tumour by the telom eric repeat amplification protocol (TRAP) assay. Matched mirror image tissue samples were taken for histological analysis of tissue adequacy , statistical correlation of telomerase with tumour histological featu res, Mib-1 (a marker for cell cycling) labelling, and p53 immunohistoc hemistry. Results-All five well differentiated oligodendrogliomas were homogeneously telomerase negative and two of three untreated anaplast ic oligodendrogliomas were homogeneously positive. In contrast, 10 of 14 high grade astrocytomas showed heterogeneity for telomerase express ion across the multiple regions sampled. All glioblastoma multiformes and two of three anaplastic astrocytomas showed at least one region po sitive for telomerase. When test samples were individually assessed in both oligodendrogliomas and high grade astrocytomas, telomerase expre ssion was associated with Mib-1 labelling (p < 0.001). For the entire group, telomerase expression was associated with grade of tumour, age of patient, and (all p < 0.001). Conclusions-This regional study clari fies that all glioblastoma multiformes are at least focally positive a nd that telomerase expression correlates with tumour grade in oligoden drogliomas. Homogeneity versus heterogeneity for telomerase expression across multiple regions of oligodendrogliomas versus high grade astro cytomas may provide important preclinical data on the use of antitelom erase agents in these adult glial tumours.