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Development of a voided urine assay for detecting prostate cancer non-invasively: a pilot study.

Authors
  • Trabulsi, Edouard J1
  • Tripathi, Sushil K2
  • Gomella, Leonard1, 3
  • Solomides, Charalambos4
  • Wickstrom, Eric3, 5
  • Thakur, Mathew L2, 3
  • 1 Department of Urology, Thomas Jefferson University, Philadelphia, PA, USA.
  • 2 Department of Radiology, Thomas Jefferson University, Philadelphia, PA, USA.
  • 3 Department of Pathology, Thomas Jefferson University, Philadelphia, PA, USA.
  • 4 Departments of Biochemistry and Molecular Biology, Thomas Jefferson University, Philadelphia, PA, USA.
  • 5 The Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, USA.
Type
Published Article
Journal
British Journal of Urology
Publisher
Wiley (Blackwell Publishing)
Publication Date
Jun 01, 2017
Volume
119
Issue
6
Pages
885–895
Identifiers
DOI: 10.1111/bju.13775
PMID: 28075510
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

To validate a hypothesis that prostate cancer can be detected non-invasively by a simple and reliable assay by targeting genomic VPAC receptors expressed on malignant prostate cancer cells shed in voided urine. VPAC receptors were targeted with a specific biomolecule, TP4303, developed in our laboratory. With an Institutional Review Board 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 (207 patients, 176 men and 31 women, aged ≥21 years) was cytospun. The cells were fixed and treated with TP4303 and 4,6-diamidino-2-phenylindole (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 a blue nucleus were regarded as 'normal'. VPAC presence was validated using receptor blocking assay and cell malignancy was confirmed by prostate cancer gene profile examination. The urine specimens were labelled 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 men with a prostate cancer diagnosis (141), and none of the 10 men with benign prostatic hyperplasia. Of the 56 'normal' patients, 62.5% (35 patients, 10 men and 25 women) were negative for VPAC cells; 19.6% (11, 11 men and no women) had VPAC positive cells; and 17.8% (10, four men and six women) were uninterpretable due to excessive crystals in the urine. Although data are limited, the sensitivity of the assay was 99.3% with a confidence interval (CI) of 96.1-100% and the specificity was 100% with a CI of 69.2-100%. Receptor blocking assay and fluorescence-activated cell sorting (FACS) analyses demonstrated the presence of VPAC receptors and gene profiling examinations confirmed that the cells expressing VPAC receptors were malignant prostate cancer cells. These preliminary data are highly encouraging and warrant further evaluation of the assay to serve as a simple and reliable tool to detect prostate cancer non-invasively. © 2017 The Authors BJU International © 2017 BJU International Published by John Wiley & Sons Ltd.

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