Profiling of Circulating microRNAs in Prostate Cancer Reveals Diagnostic Biomarker Potential

Early detection of prostate cancer (PC) is paramount as localized disease is generally curable, while metastatic PC is generally incurable. There is a need for improved, minimally invasive biomarkers as current diagnostic tools are inaccurate, leading to extensive overtreatment while still missing some clinically significant cancers. Consequently, we profiled the expression levels of 92 selected microRNAs by RT-qPCR in plasma samples from 753 patients, representing multiple stages of PC and non-cancer controls. First, we compared plasma miRNA levels in patients with benign prostatic hyperplasia (BPH) or localized prostate cancer (LPC), versus advanced prostate cancer (APC). We identified several dysregulated microRNAs with a large overlap of 59 up/down-regulated microRNAs between BPH versus APC and LPC versus APC. Besides identifying several novel PC-associated dysregulated microRNAs in plasma, we confirmed the previously reported upregulation of miR-375 and downregulation of miR-146a-5p. Next, by randomly splitting our dataset into a training and test set, we identified and successfully validated a novel four microRNA diagnostic ratio model, termed bCaP (miR-375*miR-33a-5p/miR-16-5p*miR-409-3p). Combined in a model with prostate specific antigen (PSA), digital rectal examination status, and age, bCaP predicted the outcomes of transrectal ultrasound (TRUS)-guided biopsies (negative vs. positive) with greater accuracy than PSA alone (Training: area under the curve (AUC), model = 0.84; AUC, PSA = 0.63. Test set: AUC, model = 0.67; AUC, PSA = 0.56). It may be possible in the future to use this simple and minimally invasive bCaP test in combination with existing clinical parameters for a more accurate selection of patients for prostate biopsy.

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Multiparametric ultrasound and micro-ultrasound in prostate cancer: a comprehensive review

British Journal of Radiology ◽

10.1259/bjr.20210633 ◽

2021 ◽

Author(s):

Adriano Basso Dias ◽

Ciara O’Brien ◽

Jean-Michel Correas ◽

Sangeet Ghai

Keyword(s):

Prostate Cancer ◽

Specific Antigen ◽

Transrectal Ultrasound ◽

Digital Rectal Examination ◽

High Sensitivity ◽

Cost Effective ◽

Cognitive Fusion ◽

Clinically Significant ◽

Multiparametric Ultrasound ◽

Targeted Biopsies

Prostate cancer (PCa) is the most common non-cutaneous cancer diagnosed in males. Traditional tools for screening and diagnosis, such as prostate-specific antigen, digital rectal examination and conventional transrectal ultrasound (TRUS), present low accuracy for PCa detection. Multiparametric MRI has become a game changer in the PCa diagnosis pathway and MRI-targeted biopsies are currently recommended for males at risk of clinically significant PCa, even in biopsy-naïve patients. Recent advances in ultrasound have also emerged with the goal to provide a readily accessible and cost-effective tool for detection of PCa. These newer techniques include elastography and contrast-enhanced ultrasound, as well as improved B-mode and Doppler techniques. These modalities can be combined to define a novel ultrasound approach, multiparametric ultrasound. High frequency Micro-ultrasound has emerged as a promising imaging technology for PCa diagnosis. Initial results have shown high sensitivity of Micro-ultrasound in detecting PCa in addition to its potential in improving the accuracy of targeted biopsies, based on targeting under real-time visualization, rather than relying on cognitive/fusion software MRI-transrectal ultrasound-guided biopsy.

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Performance of a Single Assay for Both Type III and Type VI TMPRSS2:ERG Fusions in Noninvasive Prediction of Prostate Biopsy Outcome

Clinical Chemistry ◽

10.1373/clinchem.2008.108845 ◽

2008 ◽

Vol 54 (12) ◽

pp. 2007-2017 ◽

Cited By ~ 22

Author(s):

Jarrod P Clark ◽

Kristofer W Munson ◽

Jessie W Gu ◽

Katarzyna Lamparska-Kupsik ◽

Kevin G Chan ◽

...

Keyword(s):

Prostate Cancer ◽

Specific Antigen ◽

Transrectal Ultrasound ◽

Digital Rectal Examination ◽

Area Under The Curve ◽

Diagnostic Value ◽

Gleason Grade ◽

Type Iii ◽

Standard Curve ◽

Institutional Review

Abstract Background: TMPRSS2:ERG fusions are promising prostate cancer biomarkers. Because they can occur in multiple forms in a single cancer specimen, we developed a quantitative PCR test that detects both type III and type VI TMPRSS2:ERG fusions. The assay is quantified from a standard curve determined with a plasmid-cloned type III TMPRSS2:ERG fusion target. Methods: We collected expressed prostatic secretion (EPS) under an institutional review board-approved, blinded, prospective study from 74 patients undergoing transrectal ultrasound-guided biopsy for prostate cancer. We compared the characteristic performance of the test for type III and type VI TMPRSS2:ERG fusions in predicting biopsy outcome and distinguishing between high and low Gleason scores with similar tests for the expression of PCA3 and DNA methylation levels of the APC, RARB, RASSF1, and GSTP1 genes. We used logistic regression to analyze the effects of multiple biomarkers in linear combinations. Results: Each test provided a significant improvement in characteristic performance over baseline digital rectal examination (DRE) plus serum prostate-specific antigen (PSA); however, the test for type III and type VI TMPRSS2:ERG fusions yielded the best performance in predicting biopsy outcome [area under the curve (AUC) 0.823, 95% CI 0.728–0.919, P < 0.001] and Gleason grade >7 (AUC 0.844, 95% CI 0.740–0.948, P < 0.001). Conclusions: Although each test appears to have diagnostic value, PSA plus DRE plus type III and type VI TMPRSS2:ERG provided the best diagnostic performance in EPS specimens.

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A multicentre randomised controlled trial assessing whether MRI-targeted biopsy is non-inferior to standard transrectal ultrasound guided biopsy for the diagnosis of clinically significant prostate cancer in men without prior biopsy: a study protocol

BMJ Open ◽

10.1136/bmjopen-2017-017863 ◽

2017 ◽

Vol 7 (10) ◽

pp. e017863 ◽

Cited By ~ 5

Author(s):

Veeru Kasivisvanathan ◽

Fatima Jichi ◽

Laurence Klotz ◽

Arnauld Villers ◽

Samir S Taneja ◽

...

Keyword(s):

Prostate Cancer ◽

Alternative Pathway ◽

Specific Antigen ◽

Transrectal Ultrasound ◽

Digital Rectal Examination ◽

Classical Pathway ◽

Targeted Biopsy ◽

Ultrasound Guided ◽

Trus Biopsy ◽

Clinically Significant

IntroductionThe classical pathway for the diagnosis of prostate cancer is transrectal ultrasound-guided (TRUS) biopsy of the prostate initiated on the basis of a raised prostate-specific antigen (PSA). An alternative pathway is to perform multi-parametricMRI (MPMRI) to localise cancer and to use this information to influence the decision for, and conduct of, a subsequent biopsy, known as an MPMRI-targeted biopsy. An MPMRI pathway has been shown to detect a similar or greater amount of clinically significant cancer as TRUS biopsy but has several advantages, including the potential to biopsy fewer men with fewer cores.MethodsThis is a pragmatic, international, multicentre, parallel group randomised study in which men are allocated in a 1:1 ratio to an MPMRI or TRUS biopsy pathway. This study will assess whether an MPMRI-targeted biopsy approach is non-inferior to a standard TRUS biopsy approach in the diagnosis of clinically significant cancer.Men in the MRI arm will undergo targeted biopsy of suspicious areas only and no biopsy will be carried out if the MRI is non-suspicious. Men in the TRUS biopsy will undergo a standard 10–12-core TRUS biopsy. The main inclusion criteria are a serum PSA ≤20 ng/mL, a digital rectal examination finding of T2 or less and no prior prostate biopsy.The primary outcome is the proportion of men with clinically significant cancer detected. A sample size of at least 470 patients is required. Key secondary outcomes include the proportion of clinically insignificant cancer detected.Ethics and disseminationEthical approval was obtained from the National Research Ethics Committee East Midlands, Leicester (15/EM/0188). Results of this study will be disseminated through national and international papers. The participants and relevant patient support groups will be informed about the results of the study.Registration detailsNCT02380027; Pre-results

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Prostate Cancer Liquid Biopsy Biomarkers’ Clinical Utility in Diagnosis and Prognosis

Cancers ◽

10.3390/cancers13133373 ◽

2021 ◽

Vol 13 (13) ◽

pp. 3373

Author(s):

Milena Matuszczak ◽

Jack A. Schalken ◽

Maciej Salagierski

Keyword(s):

Prostate Cancer ◽

Liquid Biopsy ◽

Current Knowledge ◽

Prostate Gland ◽

Specific Antigen ◽

Transrectal Ultrasound ◽

Digital Rectal Examination ◽

Cost Effective ◽

Non Invasive ◽

Diagnosis And Prognosis

Prostate cancer (PCa) is the most common cancer in men worldwide. The current gold standard for diagnosing PCa relies on a transrectal ultrasound-guided systematic core needle biopsy indicated after detection changes in a digital rectal examination (DRE) and elevated prostate-specific antigen (PSA) level in the blood serum. PSA is a marker produced by prostate cells, not just cancer cells. Therefore, an elevated PSA level may be associated with other symptoms such as benign prostatic hyperplasia or inflammation of the prostate gland. Due to this marker’s low specificity, a common problem is overdiagnosis, which leads to unnecessary biopsies and overtreatment. This is associated with various treatment complications (such as bleeding or infection) and generates unnecessary costs. Therefore, there is no doubt that the improvement of the current procedure by applying effective, sensitive and specific markers is an urgent need. Several non-invasive, cost-effective, high-accuracy liquid biopsy diagnostic biomarkers such as Progensa PCA3, MyProstateScore ExoDx, SelectMDx, PHI, 4K, Stockholm3 and ConfirmMDx have been developed in recent years. This article compares current knowledge about them and their potential application in clinical practice.

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Analysis of risk factors for determining the need for prostate biopsy in patients with negative MRI

Scientific Reports ◽

10.1038/s41598-021-83802-z ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Linghui Liang ◽

Feng Qi ◽

Yifei Cheng ◽

Lei Zhang ◽

Dongliang Cao ◽

...

Keyword(s):

Prostate Cancer ◽

Detection Efficiency ◽

Specific Antigen ◽

Digital Rectal Examination ◽

Multivariable Logistic Regression Analysis ◽

Detection Rates ◽

Prostate Biopsies ◽

Clinically Significant ◽

Definition Of ◽

Medical University

AbstractTo analyze the clinical characteristics of patients with negative biparametric magnetic resonance imaging (bpMRI) who didn’t need prostate biopsies (PBs). A total of 1,012 male patients who underwent PBs in the First Affiliated Hospital of Nanjing Medical University from March 2018 to November 2019, of 225 had prebiopsy negative bpMRI (defined as Prostate Imaging Reporting and Data System (PI-RADS 2.1) score less than 3). The detection efficiency of clinically significant prostate cancer (CSPCa) was assessed according to age, digital rectal examination (DRE), prostate volume (PV) on bpMRI, prostate-specific antigen (PSA) and PSA density (PSAD). The definition of CSPCa for Gleason score > 6. Univariate and multivariable logistic regression analysis were used to identify predictive factors of absent CSPCa on PBs. Moreover, absent CSPCa contained clinically insignificant prostate cancer (CIPCa) and benign result. The detection rates of present prostate cancer (PCa) and CSPCa were 27.11% and 16.44%, respectively. Patients who were diagnosed as CSPCa had an older age (P < 0.001), suspicious DRE (P < 0.001), a smaller PV (P < 0.001), higher PSA value (P = 0.008) and higher PSAD (P < 0.001) compared to the CIPCa group and benign result group. PSAD < 0.15 ng/ml/cm3 (P = 0.004) and suspicious DRE (P < 0.001) were independent predictors of absent CSPCa on BPs. The negative forecast value of bpMRI for BP detection of CSPCa increased with decreasing PSAD, mainly in patients with naive PB (P < 0.001) but not in prior negative PB patients. 25.33% of the men had the combination of negative bpMRI, PSAD < 0.15 ng/ml/cm3 and PB naive, and none had CSPCa on repeat PBs. The incidence of PB was determined, CSPCa was 1.59%, 0% and 16.67% in patients with negative bpMRI and PSAD < 0.15 ng/ml/cm3, patients with negative bpMRI, PSAD < 0.15 ng/ml/cm3 and biopsy naive and patients with negative bpMRI, PSAD < 0.15 ng/ml/cm3 and prior negative PB, separately. We found that a part of patients with negative bpMRI, a younger age, no suspicious DRE and PSAD < 0.15 ng/ml/cm3 may securely avoid PBs. Conversely PB should be considered in patients regardless of negative bpMRI, especially who with a greater age, obviously suspicious DRE, significantly increased PSA value, a significantly small PV on MRI and PSAD > 0.15 ng/ml/cm3.

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Histology results of systematic prostate biopsies by in-bore magnetic resonance imaging vs. transrectal ultrasound

Canadian Urological Association Journal ◽

10.5489/cuaj.6607 ◽

2020 ◽

Vol 15 (5) ◽

Author(s):

Alon Lazarovich ◽

Gil Raviv ◽

Yael Laitman ◽

Orith Portnoy ◽

Orit Raz ◽

...

Keyword(s):

Magnetic Resonance Imaging ◽

Magnetic Resonance ◽

Prostate Biopsy ◽

Specific Antigen ◽

Transrectal Ultrasound ◽

Digital Rectal Examination ◽

Resonance Imaging ◽

Rectal Examination ◽

Number Of Patients ◽

Clinically Significant

Introduction: We aimed to compare systematic biopsies (SBs) of in-bore magnetic resonance-guided prostate biopsy (MRGpB) with those performed under transrectal ultrasound (TRUS) guidance in the clinical setting. Methods: Data on all 161 consecutive patients undergoing prostate biopsy in our institution between November 2017 and July 2019 were retrospectively collected. The patients were referred to biopsy due to elevated prostate-specific antigen (PSA) and/or abnormal digital rectal examination and/or at least one Prostate Imaging Reporting and Data System (PI-RADS) lesion score of ≥3 on multiparametric magnetic resonance imaging (mpMRI). We included patients with PSA levels ≤20 ng/ml and those with 8–12 core biopsies. Histology results of SBs performed by in-bore MRGpB were compared to TRUS SBs. Chi-squared, Fischer’s exact, and multivariate Pearson regression tests were used for statistical analysis (SPSS, IBM Corporation). Results: In total, 128 patients were eligible for analysis. Their median age was 68 years (interquartile range [IQR] 61.5–72), mean prostate size 55±29 cc, and mean PSA and PSA density levels 7.6±3.5 ng/ml and 0.18±0.13 ng/ml/cc, respectively. Thirty-five patients (27.3%) had suspicious digital rectal examination findings. Both biopsy groups were similar for these parameters. Thirty-eight (62.3%) MRGpB patients had a previous biopsy vs. 5 (7.1%) TRUS-SB patients (p<0.0001). The number of patients diagnosed with clinically significant and non-significant disease was similar for both groups. High-risk disease was more prevalent in the TRUS-SB group (22.4% vs. 4.9%, p<0.01). Conclusions: Our data suggest that in-bore MRGpB is no better than TRUS for guiding SBs for the detection of clinically significant prostate cancer.

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Accuracy of Tumour-Associated Circulating Endothelial Cells as a Screening Biomarker for Clinically Significant Prostate Cancer

Cancers ◽

10.3390/cancers11081064 ◽

2019 ◽

Vol 11 (8) ◽

pp. 1064 ◽

Cited By ~ 2

Author(s):

Sebastian Chakrit Bhakdi ◽

Prapat Suriyaphol ◽

Ponpan Thaicharoen ◽

Sebastian Tobias Karl Grote ◽

Chulaluk Komoltri ◽

...

Keyword(s):

Prostate Cancer ◽

Endothelial Cells ◽

Predictive Value ◽

Specific Antigen ◽

Transrectal Ultrasound ◽

Circulating Endothelial Cells ◽

Index Test ◽

Psa Testing ◽

Diagnostic Potential ◽

Clinically Significant

Even though more than 350,000 men die from prostate cancer every year, broad-based screening for the disease remains a controversial topic. Guidelines demand that the only commonly accepted screening tool, prostate-specific antigen (PSA) testing, must be followed by prostate biopsy if results are elevated. Due to the procedure’s low positive predictive value (PPV), however, over 80% of biopsies are performed on healthy men or men with clinically insignificant cancer—prompting calls for new ways of vetting equivocal PSA readings prior to the procedure. Responding to the challenge, the present study investigated the diagnostic potential of tumour-associated circulating endothelial cells (tCECs), which have previously been described as a novel, blood-based biomarker for clinically significant cancers. Specifically, the objective was to determine the diagnostic accuracy of a tCEC-based blood test to detect clinically significant prostate cancer (defined as Gleason score ≥ 3 + 4) in high-risk patients. Performed in a blinded, prospective, single-centre set-up, it compared a novel tCEC index test with transrectal ultrasound-guided biopsy biopsy as a reference on a total of 170 patients and found that a tCEC add-on test will almost double the PPV of a standalone PSA test (32% vs. 17%; p = 0.0012), while retaining a negative predictive value above 90%.

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Independent Validation of a Diagnostic Noninvasive 3-MicroRNA Ratio Model (uCaP) for Prostate Cancer in Cell-Free Urine

Clinical Chemistry ◽

10.1373/clinchem.2018.296681 ◽

2019 ◽

Vol 65 (4) ◽

pp. 540-548 ◽

Cited By ~ 6

Author(s):

Jacob Fredsøe ◽

Anne K I Rasmussen ◽

Emma B Laursen ◽

Yunpeng Cai ◽

Kenneth A Howard ◽

...

Keyword(s):

Prostate Cancer ◽

Prostate Biopsy ◽

Specific Antigen ◽

Transrectal Ultrasound ◽

Area Under The Curve ◽

Extracellular Vesicle ◽

Urine Samples ◽

Ratio Model ◽

Psa Testing ◽

Diagnostic Potential

Abstract BACKGROUND Detection of prostate cancer (PC) based on serum prostate-specific antigen (PSA) testing leads to many unnecessary prostate biopsies, overdiagnosis, and overtreatment of clinically insignificant tumors. Thus, novel and more accurate molecular biomarkers are required. METHODS Using reverse transcription quantitative PCR, we measured the concentrations of 45 preselected microRNAs (miRNAs) in extracellular vesicle-enriched cell-free urine samples from 4 independent patient cohorts from Spain and Denmark, including 758 patients with clinically localized PC, 289 noncancer controls with benign prostatic hyperplasia (BPH), and 233 patients undergoing initial transrectal ultrasound (TRUS)-guided prostate biopsy owing to PC suspicion (101 with benign and 132 with malignant outcome). Diagnostic potential was assessed by ROC and decision curve analysis. RESULTS We identified and successfully validated 8 upregulated and 21 downregulated miRNAs in urine from PC patients. Furthermore, we validated a previously identified 3-miRNA diagnostic ratio model, uCaP (miR-222–3p*miR-24–3p/miR-30c-5p). High uCaP scores were distinctive of PC in urine samples from BPH vs PC patients in 3 independent cohorts [area under the curve (AUC) = 0.84, 0.71, 0.72]. Additionally, uCaP predicted TRUS biopsy results with greater accuracy than PSA (AUC uCaP = 0.644; AUC PSA = 0.527) for patients within the diagnostic gray zone (PSA ≤ 10 ng/mL). CONCLUSIONS We successfully validated a urine-based diagnostic 3-miRNA signature for PC (uCaP) in 3 independent patient cohorts from 2 countries. In the future, the simple and noninvasive uCaP test may be used to help more accurately select patients for prostate biopsy. Prospective clinical validation is warranted.

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The Association of PSA-IGM and Total PSA Improves the Diagnosis of Prostate Cancer

The International Journal of Biological Markers ◽

10.1177/172460080902400338 ◽

2009 ◽

Vol 24 (3) ◽

pp. 212-212

Author(s):

Danilo Zani ◽

Silvia Costa ◽

Lorenzo Gatti ◽

Nicola Pesenti ◽

Alberto Pettenò ◽

...

Keyword(s):

Prostate Cancer ◽

Diagnostic Accuracy ◽

Prostate Biopsy ◽

Specific Antigen ◽

Digital Rectal Examination ◽

Serum Levels ◽

Immunoglobulin M ◽

Diagnostic Tools ◽

Psa Test ◽

Total Psa

Background and aim The specific causes of prostate cancer (Pca) are unknown but the main risk factors of tumor development are associated with age, genetic factors, ethnicity, diet and lifestyle. Prostate cancer is rare in men under 45 years of age, but becomes more common with advancing age. The main diagnostic tools for demonstrating the presence of PCa include digital rectal examination, transrectal ultrasonography, and serum measurement of prostate specific antigen (PSA) followed by prostate biopsy for confirmation of the diagnosis. While the measurement of PSA levels has revolutionized the diagnosis of PCa, it has also increased its overdiagnosis due to the poor diagnostic accuracy. Scientific evidence indicates that biomarkers for different types of cancer such as liver and colorectal cancer circulate in the blood associated with immunoglobulin M (IgM) to form complexes that allow a better diagnosis in comparison to circulating free biomarkers. In prostate cancer it has been demonstrated that testing for serum levels of the PSA-IgM immune complex improves the diagnostic performance of total PSA. The aim of this study was to evaluate the diagnostic accuracy of PSA-IgM compared to total PSA for the selection of patients to be submitted to transrectal ultrasound-guided prostate biopsy. Patients and methods Serum samples from 67 male patients, 33 affected by PCa with a Gleason score from 5 to 7, and 34 affected by benign prostate hypertrophy (BPH), were collected by the Department of Urology of the Spedali Civili of Brescia. The samples were immediately snap frozen at −80°C. Serum levels of PSA-IgM were assessed using Prostate-IC (Xeptagen, Italy) while PSA levels were determined with the Immulite 2000 of Medical Systems S.p.A. Results Patients were stratified into 2 groups according to age; the first group consisted of 24 patients with PCa and 20 with BPH aged between 60 and 70 years and the second group consisted of 9 patients with PCa and 14 with BPH aged between 70 and 80 years. Serum levels of PSA and PSA-IgM were analyzed in the 2 groups using cutoff values of 4 ng/mL for PSA and 145 AU/mL for PSA-IgM. In the first group, 1 8 of 24 PCa patients were positive for PSA (75% sensitivity) with a specificity of 50% (10 of 20 BPH patients), and 1 0 of 24 PCa patients were positive with the PSA-IgM assay (42% sensitivity), which had a higher specificity (70%; 6 of 20 BPH patients). The combination of both biomarkers resulted in a sensitivity of 38% (9 of 24 patients with PCa) but showed a significant improvement in specificity up to 90%, since 18 of 20 patients with BPH were negative for at least one test. In the second group of patients aged 70 to 80 years, the PSA test had a sensitivity of 67% (6/9 PCa patients) and a specificity of 78% (3/14 BPH patients) compared with a sensitivity of 44% for the PSA-IgM test (4/9 PCa patients) with a specificity of 71% (4/14 BPH patients). The combination of PSA and PSA-IgM had a sensitivity of 30% (3/9) but the highest specificity (93%, 13/14 BPH patients). Conclusion The results of the study demonstrate the diagnostic value of the PSA-IgM assay compared with the total PSA test. The combination of PSA-IgM with total PSA was the best approach to reduce the number of false-positive results, thus improving the diagnosis of prostate cancer.

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APTIMA PCA3 Molecular Urine Test: Development of a Method to Aid in the Diagnosis of Prostate Cancer

Clinical Chemistry ◽

10.1373/clinchem.2005.063289 ◽

2006 ◽

Vol 52 (6) ◽

pp. 1089-1095 ◽

Cited By ~ 340

Author(s):

Jack Groskopf ◽

Sheila MJ Aubin ◽

Ina Lim Deras ◽

Amy Blase ◽

Sharon Bodrug ◽

...

Keyword(s):

Prostate Cancer ◽

Prostate Biopsy ◽

Specific Antigen ◽

Digital Rectal Examination ◽

Prostate Cancer Risk ◽

Area Under The Curve ◽

Roc Curve Analysis ◽

Cancer Risk Factors ◽

Specimen Processing ◽

Whole Urine

Abstract Background: Prostate cancer gene 3 (PCA3) encodes a prostate-specific mRNA that has shown promise as a prostate cancer diagnostic tool. This report describes the characterization of a prototype quantitative PCA3-based test for whole urine. Methods: Whole-urine specimens were collected after digital rectal examination from 3 groups: men scheduled for prostate biopsy (n = 70), healthy men (<45 years of age with no known prostate cancer risk factors; n = 52), and men who had undergone radical prostatectomy (n = 21). PCA3 and prostate-specific antigen (PSA) mRNAs were isolated, amplified, and quantified by use of Gen-Probe DTS400® Systems. Prostate biopsy results were correlated with the PCA3/PSA mRNA ratio, and PSA mRNA concentrations were used to normalize PCA3 signals and confirm the yield of prostate-specific RNA. Assay precision, specimen stability, and mRNA yield were also evaluated. Results: The specimen informative rate (fraction of specimens yielding sufficient RNA for analysis) was 98.2%. In this clinical research study, ROC curve analysis of prebiopsy specimens yielded an area under the curve of 0.746; sensitivity was 69% and specificity 79%. Serum PSA assay specificity was 28% for this same group. PCA3 and PSA mRNAs were undetectable in postprostatectomy specimens except for one man with recurrent prostate cancer. Assay interrun CVs were ≤12%. Both mRNAs were stable in processed urine up to 5 days at 4 °C and after 5 freeze–thaw cycles. Conclusion: The APTIMA® PCA3 assay combines simple specimen processing with precise assays and existing instruments and could add specificity to the current algorithm for prostate cancer diagnosis.

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