Skip to main content
Top
Published in: World Journal of Urology 5/2011

Open Access 01-10-2011 | Original Article

PCA3 molecular urine assay for prostate cancer: association with pathologic features and impact of collection protocols

Authors: Michael A. Liss, Rosanne Santos, Kathryn Osann, Alice Lau, Thomas E. Ahlering, David K. Ornstein

Published in: World Journal of Urology | Issue 5/2011

Login to get access

Abstract

Introduction

PCA3 is a non-coding mRNA molecule that is overexpressed in prostate cancer. The purpose of this study is to evaluate the utility of the PCA3 molecular urine test scores to predict adverse pathologic features and catheterized specimen collection.

Methods

Hundred men with clinically localized prostate cancer scheduled to undergo robotic prostatectomy were enrolled in the study following a standard consent process. The study protocol consisted of providing four urine samples. Voided urine obtained following digital rectal examination (DRE) pre-operatively (Vl), catheterized urine without DRE (V2), and l0-day and 6-week postoperative voided (V3 and V4) urine samples were collected and analyzed. These four urine specimens underwent target capture, transcription-mediated amplification, and hybridization in order to quantify both PCA3 and PSA mRNA. The PCA3 score was calculated as the ratio of PCA3 to PSA.

Results

Informative rates (sufficient mRNA for analysis) for VI, V2, V3 and V4 were 91, 85, 0 and 2%, respectively. There was no significant associations with pathological stage, Gleason score >6. Higher PCA3 scores at V1 correlated with increased risk for perineural invasion (P = 0.0479).

Conclusions

Informative PCA3 scores can be obtained from post-DRE voided urine as well as catheterized urine without a DRE. The PCA3 test does not seem to predict adverse pathologic features, though, may have an association with perineural invasion. The ability of PCA3 score to predict clinical outcome remains to be determined.
Literature
2.
go back to reference Hugosson J, Carlsson S, Aus G, Bergdahl S, Khatami A, Lodding P, Pihl CG, Stranne J, Holmberg E, Lilja H (2010) Mortality results from the Goteborg randomised population-based prostate-cancer screening trial. Lancet Oncol 11(8):725–732. doi:10.1016/S1470-2045(10)70146-7 PubMedCrossRef Hugosson J, Carlsson S, Aus G, Bergdahl S, Khatami A, Lodding P, Pihl CG, Stranne J, Holmberg E, Lilja H (2010) Mortality results from the Goteborg randomised population-based prostate-cancer screening trial. Lancet Oncol 11(8):725–732. doi:10.​1016/​S1470-2045(10)70146-7 PubMedCrossRef
3.
go back to reference Schroder FH, Hugosson J, Roobol MJ, Tammela TL, Ciatto S, Nelen V, Kwiatkowski M, Lujan M, Lilja H, Zappa M, Denis LJ, Recker F, Berenguer A, Maattanen L, Bangma CH, Aus G, Villers A, Rebillard X, van der Kwast T, Blijenberg BG, Moss SM, de Koning HJ, Auvinen A (2009) Screening and prostate-cancer mortality in a randomized European study. N Engl J Med 360(13):1320–1328. doi:10.1056/NEJMoa0810084 PubMedCrossRef Schroder FH, Hugosson J, Roobol MJ, Tammela TL, Ciatto S, Nelen V, Kwiatkowski M, Lujan M, Lilja H, Zappa M, Denis LJ, Recker F, Berenguer A, Maattanen L, Bangma CH, Aus G, Villers A, Rebillard X, van der Kwast T, Blijenberg BG, Moss SM, de Koning HJ, Auvinen A (2009) Screening and prostate-cancer mortality in a randomized European study. N Engl J Med 360(13):1320–1328. doi:10.​1056/​NEJMoa0810084 PubMedCrossRef
4.
go back to reference Babaian RJ, Johnston DA, Naccarato W, Ayala A, Bhadkamkar VA, Fritsche HH Jr (2001) The incidence of prostate cancer in a screening population with a serum prostate specific antigen between 2.5 and 4.0 ng/ml: relation to biopsy strategy. J Urol 165(3):757–760PubMedCrossRef Babaian RJ, Johnston DA, Naccarato W, Ayala A, Bhadkamkar VA, Fritsche HH Jr (2001) The incidence of prostate cancer in a screening population with a serum prostate specific antigen between 2.5 and 4.0 ng/ml: relation to biopsy strategy. J Urol 165(3):757–760PubMedCrossRef
5.
go back to reference Catalona WJ, Smith DS, Ornstein DK (1997) Prostate cancer detection in men with serum PSA concentrations of 2.6 to 4.0 ng/mL and benign prostate examination. Enhancement of specificity with free PSA measurements. JAMA 277(18):1452–1455PubMedCrossRef Catalona WJ, Smith DS, Ornstein DK (1997) Prostate cancer detection in men with serum PSA concentrations of 2.6 to 4.0 ng/mL and benign prostate examination. Enhancement of specificity with free PSA measurements. JAMA 277(18):1452–1455PubMedCrossRef
6.
go back to reference Hessels D, Klein Gunnewiek JM, van Oort I, Karthaus HF, van Leenders GJ, van Balken B, Kiemeney LA, Witjes JA, Schalken JA (2003) DD3(PCA3)-based molecular urine analysis for the diagnosis of prostate cancer. Eur Urol 44(1):8–15; discussion 15–16PubMedCrossRef Hessels D, Klein Gunnewiek JM, van Oort I, Karthaus HF, van Leenders GJ, van Balken B, Kiemeney LA, Witjes JA, Schalken JA (2003) DD3(PCA3)-based molecular urine analysis for the diagnosis of prostate cancer. Eur Urol 44(1):8–15; discussion 15–16PubMedCrossRef
7.
go back to reference de Kok JB, Verhaegh GW, Roelofs RW, Hessels D, Kiemeney LA, Aalders TW, Swinkels DW, Schalken JA (2002) DD3(PCA3), a very sensitive and specific marker to detect prostate tumors. Cancer Res 62(9):2695–2698PubMed de Kok JB, Verhaegh GW, Roelofs RW, Hessels D, Kiemeney LA, Aalders TW, Swinkels DW, Schalken JA (2002) DD3(PCA3), a very sensitive and specific marker to detect prostate tumors. Cancer Res 62(9):2695–2698PubMed
8.
go back to reference Fradet Y, Saad F, Aprikian A, Dessureault J, Elhilali M, Trudel C, Masse B, Piche L, Chypre C (2004) uPM3, a new molecular urine test for the detection of prostate cancer. Urology 64(2): 311–315; discussion 315–316. doi:10.1016/j.urology.2004.03.052 Fradet Y, Saad F, Aprikian A, Dessureault J, Elhilali M, Trudel C, Masse B, Piche L, Chypre C (2004) uPM3, a new molecular urine test for the detection of prostate cancer. Urology 64(2): 311–315; discussion 315–316. doi:10.​1016/​j.​urology.​2004.​03.​052
9.
10.
go back to reference Whitman EJ, Groskopf J, Ali A, Chen Y, Blase A, Furusato B, Petrovics G, Ibrahim M, Elsamanoudi S, Cullen J, Sesterhenn IA, Brassell S, Rittenhouse H, Srivastava S, McLeod DG (2008) PCA3 score before radical prostatectomy predicts extracapsular extension and tumor volume. J Urol 180(5):1975–1978; discussion 1978–1979. doi:10.1016/j.juro.2008.07.060 Whitman EJ, Groskopf J, Ali A, Chen Y, Blase A, Furusato B, Petrovics G, Ibrahim M, Elsamanoudi S, Cullen J, Sesterhenn IA, Brassell S, Rittenhouse H, Srivastava S, McLeod DG (2008) PCA3 score before radical prostatectomy predicts extracapsular extension and tumor volume. J Urol 180(5):1975–1978; discussion 1978–1979. doi:10.​1016/​j.​juro.​2008.​07.​060
11.
go back to reference Nakanishi H, Groskopf J, Fritsche HA, Bhadkamkar V, Blase A, Kumar SV, Davis JW, Troncoso P, Rittenhouse H, Babaian RJ (2008) PCA3 molecular urine assay correlates with prostate cancer tumor volume: implication in selecting candidates for active surveillance. J Urol 179(5):1804–1809; discussion 1809–1810. doi:10.1016/j.juro.2008.01.013 Nakanishi H, Groskopf J, Fritsche HA, Bhadkamkar V, Blase A, Kumar SV, Davis JW, Troncoso P, Rittenhouse H, Babaian RJ (2008) PCA3 molecular urine assay correlates with prostate cancer tumor volume: implication in selecting candidates for active surveillance. J Urol 179(5):1804–1809; discussion 1809–1810. doi:10.​1016/​j.​juro.​2008.​01.​013
12.
go back to reference Flemming I, Cooper JS, Henson DE, et al, eds. (1998) AJCC cancer staging manual. 5 ed Flemming I, Cooper JS, Henson DE, et al, eds. (1998) AJCC cancer staging manual. 5 ed
13.
go back to reference Hessels D, van Gils MP, van Hooij O, Jannink SA, Witjes JA, Verhaegh GW, Schalken JA (2010) Predictive value of PCA3 in urinary sediments in determining clinico-pathological characteristics of prostate cancer. Prostate 70(1):10–16. doi:10.1002/pros.21032 PubMedCrossRef Hessels D, van Gils MP, van Hooij O, Jannink SA, Witjes JA, Verhaegh GW, Schalken JA (2010) Predictive value of PCA3 in urinary sediments in determining clinico-pathological characteristics of prostate cancer. Prostate 70(1):10–16. doi:10.​1002/​pros.​21032 PubMedCrossRef
14.
go back to reference van Gils MP, Hessels D, Hulsbergen-van de Kaa CA, Witjes JA, Jansen CF, Mulders PF, Rittenhouse HG, Schalken JA (2008) Detailed analysis of histopathological parameters in radical prostatectomy specimens and PCA3 urine test results. Prostate 68(11):1215–1222. doi:10.1002/pros.20781 PubMedCrossRef van Gils MP, Hessels D, Hulsbergen-van de Kaa CA, Witjes JA, Jansen CF, Mulders PF, Rittenhouse HG, Schalken JA (2008) Detailed analysis of histopathological parameters in radical prostatectomy specimens and PCA3 urine test results. Prostate 68(11):1215–1222. doi:10.​1002/​pros.​20781 PubMedCrossRef
16.
go back to reference D’Amico AV, Wu Y, Chen MH, Nash M, Renshaw AA, Richie JP (2001) Perineural invasion as a predictor of biochemical outcome following radical prostatectomy for select men with clinically localized prostate cancer. J Urol 165(1):126–129. doi:10.1097/00005392-200101000-00031 PubMedCrossRef D’Amico AV, Wu Y, Chen MH, Nash M, Renshaw AA, Richie JP (2001) Perineural invasion as a predictor of biochemical outcome following radical prostatectomy for select men with clinically localized prostate cancer. J Urol 165(1):126–129. doi:10.​1097/​00005392-200101000-00031 PubMedCrossRef
18.
go back to reference Harnden P, Shelley MD, Clements H, Coles B, Tyndale-Biscoe RS, Naylor B, Mason MD (2007) The prognostic significance of perineural invasion in prostatic cancer biopsies: a systematic review. Cancer 109(1):13–24. doi:10.1002/cncr.22388 PubMedCrossRef Harnden P, Shelley MD, Clements H, Coles B, Tyndale-Biscoe RS, Naylor B, Mason MD (2007) The prognostic significance of perineural invasion in prostatic cancer biopsies: a systematic review. Cancer 109(1):13–24. doi:10.​1002/​cncr.​22388 PubMedCrossRef
19.
go back to reference O’Malley KJ, Pound CR, Walsh PC, Epstein JI, Partin AW (2002) Influence of biopsy perineural invasion on long-term biochemical disease-free survival after radical prostatectomy. Urology 59(1):85–90PubMedCrossRef O’Malley KJ, Pound CR, Walsh PC, Epstein JI, Partin AW (2002) Influence of biopsy perineural invasion on long-term biochemical disease-free survival after radical prostatectomy. Urology 59(1):85–90PubMedCrossRef
20.
go back to reference Catalona WJ, Southwick PC, Slawin KM, Partin AW, Brawer MK, Flanigan RC, Patel A, Richie JP, Walsh PC, Scardino PT, Lange PH, Gasior GH, Loveland KG, Bray KR (2000) Comparison of percent free PSA, PSA density, and age-specific PSA cutoffs for prostate cancer detection and staging. Urology 56(2):255–260PubMedCrossRef Catalona WJ, Southwick PC, Slawin KM, Partin AW, Brawer MK, Flanigan RC, Patel A, Richie JP, Walsh PC, Scardino PT, Lange PH, Gasior GH, Loveland KG, Bray KR (2000) Comparison of percent free PSA, PSA density, and age-specific PSA cutoffs for prostate cancer detection and staging. Urology 56(2):255–260PubMedCrossRef
21.
go back to reference Brassell SA, Kao TC, Sun L, Moul JW (2005) Prostate-specific antigen versus prostate-specific antigen density as predictor of tumor volume, margin status, pathologic stage, and biochemical recurrence of prostate cancer. Urology 66(6):1229–1233. doi:10.1016/j.urology.2005.06.106 PubMedCrossRef Brassell SA, Kao TC, Sun L, Moul JW (2005) Prostate-specific antigen versus prostate-specific antigen density as predictor of tumor volume, margin status, pathologic stage, and biochemical recurrence of prostate cancer. Urology 66(6):1229–1233. doi:10.​1016/​j.​urology.​2005.​06.​106 PubMedCrossRef
22.
go back to reference Groskopf J, Aubin SM, Deras IL, Blase A, Bodrug S, Clark C, Brentano S, Mathis J, Pham J, Meyer T, Cass M, Hodge P, Macairan ML, Marks LS, Rittenhouse H (2006) APTIMA PCA3 molecular urine test: development of a method to aid in the diagnosis of prostate cancer. Clin Chem 52(6):1089–1095. doi:10.1373/clinchem.2005.063289 PubMedCrossRef Groskopf J, Aubin SM, Deras IL, Blase A, Bodrug S, Clark C, Brentano S, Mathis J, Pham J, Meyer T, Cass M, Hodge P, Macairan ML, Marks LS, Rittenhouse H (2006) APTIMA PCA3 molecular urine test: development of a method to aid in the diagnosis of prostate cancer. Clin Chem 52(6):1089–1095. doi:10.​1373/​clinchem.​2005.​063289 PubMedCrossRef
23.
go back to reference van Gils MP, Hessels D, Peelen WP, Vergunst H, Mulders PF, Schalken JA (2009) Preliminary evaluation of the effect of dutasteride on PCA3 in post-DRE urine sediments: a randomized, open-label, parallel-group pilot study. Prostate 69(15):1624–1634. doi:10.1002/pros.21011 PubMedCrossRef van Gils MP, Hessels D, Peelen WP, Vergunst H, Mulders PF, Schalken JA (2009) Preliminary evaluation of the effect of dutasteride on PCA3 in post-DRE urine sediments: a randomized, open-label, parallel-group pilot study. Prostate 69(15):1624–1634. doi:10.​1002/​pros.​21011 PubMedCrossRef
Metadata
Title
PCA3 molecular urine assay for prostate cancer: association with pathologic features and impact of collection protocols
Authors
Michael A. Liss
Rosanne Santos
Kathryn Osann
Alice Lau
Thomas E. Ahlering
David K. Ornstein
Publication date
01-10-2011
Publisher
Springer-Verlag
Published in
World Journal of Urology / Issue 5/2011
Print ISSN: 0724-4983
Electronic ISSN: 1433-8726
DOI
https://doi.org/10.1007/s00345-010-0623-6

Other articles of this Issue 5/2011

World Journal of Urology 5/2011 Go to the issue