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Noninvasive Detection of Prostate Cancer by Quantitative Analysis of Telomerase Activity

Authors' Affiliations: Departments of ¹ Surgery/Surgical Oncology and ² Urology, State University of New York at Stony Brook, Stony Brook, New York

Requests for reprints: Galina I. Botchkina, Department of Surgery/Surgical Oncology, HSC-18, Room 050, State University of New York at Stony Brook, Stony Brook, NY 11794-8191. Phone: 631-444-2076; Fax: 631-444-6348; E-mail: gbotchkina{at}notes.cc.sunysb.edu.

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.

Key Words: Exfoliated cells • immunomagnetic separation • real-time PCR