To validate a hypothesis that prostate cancer (PCa) can be detected noninvasively by a simple and reliable assay by targeting genomic VPAC receptors expressed on malignant PCa cells shed in voided urine.
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VPAC receptors were targeted with a specific biomolecule, TP4303, developed in our laboratory. With an IRB "exempt" approval of use of de-identified discarded samples, an aliquot of urine collected as a standard of care, from patients presenting to the urology clinic, (N=207, M= 176, F= 31, 21 years or older) was cytospun. The cells were fixed and treated with TP4303 and 4, 6 Dimidino-2-phenylindole, Dihydrochloride (DAPI). The cells were then observed under a microscope and cells with TP4303 orange fluorescence around the blue (DAPI) nucleus were considered malignant and those only with blue nucleus were regarded as normal. VPAC presence was validated using receptor blocking assay and cell malignancy was confirmed by PCa gene profile examination.
The urine specimens were labeled only with gender and presenting diagnosis, with no personal health identifiers or other clinical data. The assay detected VPAC positive cells in 98.6% of the patients having a PCa diagnosis, (N=141), and none (0%) of the males with benign prostatic hyperplasia (BPH) (N=10). Of the 56 "normal" patients, 62.5% (N=35, M=10, F=25) were negative for VPAC cells; 19.6% (N=11, M=11, F=0) had VPAC positive cells; and 17.8% (N=10, M=4, F=6) were uninterpretable due to excessive crystals in the urine. Although data are limited, the sensitivity of the assay was 99.3% with confidence interval of 96.1%-100% and the specificity was 100% with confidence interval of 69.2%-100%. Receptor blocking assay and FACS analyses demonstrated the presence of VPAC receptors and gene profiling examinations confirmed that the cells expressing VPAC receptors were malignant PCa cells.
These preliminary data are highly encouraging and warrant further evaluation of the assay to serve as a simple and reliable tool to detect PCa noninvasively. This article is protected by copyright. All rights reserved.
BJU international. 2017 Jan 11 [Epub ahead of print]
Edouard J Trabulsi, Sushil K Tripathi, Leonard Gomella, Charalambos Solomides, Eric Wickstrom, Mathew L Thakur
Thomas Jefferson University, Departments of Urology., Thomas Jefferson University, Departments of Radiology., Thomas Jefferson University, Departments of Pathology., Thomas Jefferson University, Departments of Biochemistry and Molecular Biology.