Focal intratumoral heterogeneity for telomerase activity in human prostatecancer

Purpose: The value of telomerase activity as a marker in clinical decision- making is closely related to how representative the analysis of a small tum or sample is for the whole tumor. We therefore evaluated the intratumoral d istribution pattern of telomerase activity in prostatic carcinomas. Materials and Methods: From 50 prostate cancer patients treated with radica l prostatectomy, telomerase activity was determined using the telomeric rep eat amplification protocol (TRAP assay). Comparative analysis of at least t wo separate cancer areas from a single tumor was performed in 42 cases. Results: Telomerase activation has been demonstrated in 90% of the prostati c carcinomas. Focal intratumoral heterogeneity was found in 38.1% of the tu mors with at least two different areas examined. Telomerase positivity of a ll samples from one given tumor was detected in 50%, telomerase negativity of all samples in 11.9%. A heterogeneous telomerase activity pattern was mo re frequently detected in tumors with a Gleason score less than or equal to 7 than in those with a Gleason score >7. Furthermore, there was an increas e in the proportion of homogeneously telomerase-positive tumors with increa se in severity of the Gleason score. The differences reached statistical si gnificance. Telomerase activity was also detected in non-cancerous prostati c tissue samples. Conclusions: Telomerase activation is nearly ubiquitous in prostatic carcin omas, although a heterogeneous telomerase activity pattern within tumors mi ght produce a false-negative result in the telomerase activity assay. This limits the value of telomerase activity assays for diagnostic means. There is evidence for a shift from telomerase-negative prostate cancer tissue tow ard telomerase positivity during the progression process of prostate cancer . The relatively high proportion of telomerase-positive nonmalignant prosta tic tissue samples argues against cancer-specificity of telomerase activati on.