Specific Detection of Prostate Cancer Cells in Urine by RNA In Situ Hybridization

Jillian N. Eskra, Daniel Rabizadeh, Jiayi Zhang, William B. Isaacs, Jun Luo, Christian P. Pavlovich

Research output: Contribution to journalArticlepeer-review

Abstract

PURPOSE: Noninvasive tests that can accurately detect prostate cancer are urgently needed for prostate cancer diagnosis, surveillance and prognosis. Exfoliated prostate cells captured in urine represent a promising resource for noninvasive detection of prostate cancer. We investigated performance of a novel cell-based urine test for detection of clinically significant prostate cancer. MATERIALS AND METHODS: We previously developed a multiplex RNA in situ hybridization assay targeting NKX3-1, PRAC1 and PCA3 that enables identification and quantification of malignant and benign prostate cells released into urine. We investigated application of the assay for prostate cancer detection in a cohort of 98 patients suspected of harboring prostate cancer. Urine was collected following digital rectal examination, and the sediment was isolated and evaluated by RNA in situ hybridization. Samples were scored based on cellular expression of RNA in situ hybridization targets. Cells of prostate origin were defined by positivity for NKX3-1 and/or PRAC1, and prostate cancer cells by positivity for PCA3. RESULTS: Prostate cells (NKX3-1/PRAC1+ cells) were detected in 69 samples, among which 20 were positive for PCA3 (ie positive for prostate cancer cells). Comparison of RNA in situ hybridization results with biopsy outcome and clinical variables revealed that positivity for cancer by RNA in situ hybridization significantly correlated with intermediate/high risk cancer (p=0.003), PSA density (p=0.022), significant disease (p <0.0001) and Gleason score (p=0.003). The test was 95% specific and 51% sensitive for detection of clinically significant prostate cancer. CONCLUSIONS: Identification of exfoliated prostate cancer cells in urine by RNA in situ hybridization provides a novel tool for highly specific and noninvasive detection of prostate cancer.

Original languageEnglish (US)
Pages (from-to)37-43
Number of pages7
JournalThe Journal of urology
Volume206
Issue number1
DOIs
StatePublished - Jul 1 2021

Keywords

  • biomarkers
  • cell biology
  • in situ hybridization
  • prostatic neoplasms
  • urine

ASJC Scopus subject areas

  • Urology

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