Noninvasive Detection of Prostate Cancer by Quantitative Analysis of Telomerase Activity

Abstract

Purpose: Prostate cancer is the most common male malignancy and the second leading cause of male cancer death; therefore, there is urgent necessity for noninvasive assays for early detection of prostate cancer. Obtaining prostate tumor samples surgically is problematic because the malignancy is heterogeneous and multifocal and early-stage tumors are nonpalpable. In contrast, exfoliated cells represent the cancer status of the entire gland better due to the general tendency of cancer cells to exfoliate into biological fluids. The purpose of this study was to clarify whether quantitative analysis of telomerase activity in exfoliated cells in urine could serve as a reliable molecular marker of prostate malignancy. Experimental Design: We analyzed prospectively post-prostatic examination^exfoliated cells from the urine of 56 patients undergoing routine prostate screening. Epithelial cells were isolated and enriched by immunomagnetic separation. Telomerase activity was analyzed by quantitative real-time PCR telomeric-repeat amplification protocol assay using Opticon MJ research instrument. Results: We report now that all prostate cancer patients revealed high levels of telomerase activity thereby showing 100% of the assay sensitivity. In contrast, the majority of patients with clinically confirmed benign prostatic hyperplasia (BPH) did not express any telomerase activity (70% of all BPH patients), most likely presenting cancer-free cases, or expressed low levels of activity (18%). However, about 12% of BPH patients revealed high levels of telomerase activity that potentially can reflect hidden prostate cancer. Conclusions: We suggest that the quantitative analysis of telomerase activity can be useful for the selection of prostate cancer and cancer-free cases.Prostate cancer is the most common male malignancy and the second leading cause of male cancer-related death (1, 2). Small prostatic carcinomas were detected in 30% of men ages 30 to 49 years, 40% of males over age 50, and 64% of men ages 60 to 70 years (3 -5). For this reason, an annual screening is generally recommended for all men over the age of 50.

Telomerase as an Important Target of Androgen Signaling Blockade for Prostate Cancer Treatment

“…Blocking telomerase activation by anti-androgen and MSA through suppressing AR signaling could thus represent an effective and selective treatment modality to target prostate cancer cells. In addition, hTERT/telomerase could be measured in blood and urine (49,50), and therefore could serve as a non-invasive, tumor-specific, functionally relevant molecular biomarker for monitoring the efficacy of the intervention.…”

Beyond prostate-specific antigen: alternate serum markers

“…[137][138][139][140] Quantitative assays for the detection of these genes in serum could serve as potentially valuable tools. Antibody array profiling has also identified possible serum markers, such as thrombospondin-1, that may differentiate between benign and malignant disease.…”

Spindle cells from AIDS-associated Kaposi's sarcoma lesions express telomerase activity that is enhanced by Kaposi's sarcoma progression factors

“…Noteworthy, the intensity of telomerase activity in tumor specimens directly relates to tumor cell growth and invasiveness, thus parallelling, at least in certain tumor types, the different stages of cancer progression (2,6,9,21,22). In addition, telomerase appears to distinguish benign hyperplasia from cancer (23,24). Previous studies indicated that active telomerase is present in lesions from AIDS-KS (12), an angioproliferative disease which can evolve into an aggressive sarcoma (10).…”