PCA3 Score Before Radical Prostatectomy Predicts Extracapsular Extension and Tumor Volume
ABSTRACT PCA3 is a prostate specific, nonprotein coding RNA that is over expressed in prostate cancer. Recent studies showed the diagnostic potential of a urine based PCA3 for predicting biopsy outcome. We assessed the relationship between urine PCA3 and pathological features in whole mount radical prostatectomy specimens.
Post-digital rectal examination urine specimens were obtained from 72 men with prostate cancer before radical prostatectomy. PCA3 and PSA mRNA were measured. The ratio of PCA3 to PSA mRNA was recorded as a PCA3 score and correlated with data on each prostate specimen.
Patients with extracapsular extension had a significantly higher median PCA3 score than patients without extracapsular extension (48.8 vs 18.7, p = 0.02). PCA3 score significantly correlated with total tumor volume (r = 0.38, p <0.01). On multivariate analysis PCA3 score was an independent predictor of extracapsular extension (p = 0.01) and total tumor volume less than 0.5 cc (p = 0.04). At a cutoff PCA3 score of 47 extracapsular extension was predicted with 94% specificity and an 80% positive predictive value. When combined with serum PSA and biopsy Gleason score, the ROC AUC for predicting extracapsular extension was 0.90.
PCA3 detected in the post-digital rectal examination urine of patients with prostate cancer correlated with pathological findings. Therefore, it could provide prognostic information. To our knowledge this is the first report of a molecular urine assay that predicts extracapsular extension.
SourceAvailable from: John R Prensner[Show abstract] [Hide abstract]
ABSTRACT: Long noncoding RNAs (lncRNAs) are an emerging class of oncogenic molecules implicated in a diverse range of human malignancies. We recently identified SChLAP1 as a novel lncRNA that demonstrates outlier expression in a subset of prostate cancers, promotes tumor cell invasion and metastasis, and associates with lethal disease. Based on these findings, we sought to develop an RNA in situ hybridization (ISH) assay for SChLAP1 to 1) investigate the spectrum of SChLAP1 expression from benign prostatic tissue to metastatic castration-resistant prostate cancer and 2) to determine whether SChLAP1 expression by ISH is associated with outcome after radical prostatectomy in patients with clinically localized disease. The results from our current study demonstrate that SChLAP1 expression increases with prostate cancer progression, and high SChLAP1 expression by ISH is associated with poor outcome after radical prostatectomy in patients with clinically localized prostate cancer by both univariate (hazard ratio = 2.343, P = .005) and multivariate (hazard ratio = 1.99, P = .032) Cox regression analyses. This study highlights a potential clinical utility for SChLAP1 ISH as a novel tissue-based biomarker assay for outcome prognostication after radical prostatectomy.Neoplasia (New York, N.Y.) 12/2014; 16(12). DOI:10.1016/j.neo.2014.11.006 · 5.40 Impact Factor
[Show abstract] [Hide abstract]
ABSTRACT: To validate post-transrectal ultrasonography (TRUS) prostate biopsy (bx) urine samples for PCA3 messenger ribonucleic acid testing, including correlation of PCA3 score with concurrent bx findings. From July 2008 to July 2010, 2015 patients had urine collected immediately after a TRUS-guided prostate bx. Excluded were men with history of prostate carcinoma (CaP), <6 or ≥24 bx cores, and/or prostate-specific antigen (PSA) level ≥50 ng/mL, resulting in 1909 included men. PCA3 and PSA messenger ribonucleic acid were quantitated using transcription-mediated amplification. A PCA3 score of ≥35 was considered positive. Mean and median ages were 66 years. Mean and median PSA levels were 6.7 and 5.1 ng/mL, respectively. Bxs were benign in 970 (50.8%), CaP in 726 (38%), high-grade prostatic intraepithelial neoplasia (HGPIN) in 124 (6.5%), and atypical in 89 (4.7%). PCA3 test was informative in 1887 (98.8%) patients. Means ± standard deviations (median) of PCA3 scores for benign, HGPIN, atypical, and CaP were 22.3 ± 27.9 (12.8), 37.6 ± 43.2 (24.1), 35.7 ± 36.2 (25.7), and 46.9 ± 48.1 (31.6; P <.05 benign vs CaP, benign vs HGPIN and atypical, HGPIN and atypical vs CaP). Sensitivity and specificity of PCA3 for CaP were 46.3% and 78.7%, respectively. CaP risk increased with progressively higher PCA3 score ranges from 14.8% for PCA3 <5 to 66.7% for PCA3 >100. Area under the curve (AUC) for the PCA3 receiver operating characteristics was not significantly different in men without prior bx (AUC = 0.716) compared with men with at least 1 prior nonpositive bx (AUC = 0.702). Post-TRUS bx urine is a valid sample for PCA3 testing. Patients with a negative bx and a positive PCA3 test may have a higher likelihood of unsampled CaP. Copyright © 2014 Elsevier Inc. All rights reserved.Urology 11/2014; 84(5):1172-80. DOI:10.1016/j.urology.2014.05.067 · 2.13 Impact Factor
[Show abstract] [Hide abstract]
ABSTRACT: Prostate cancer is one of the leading causes of mortality among US males. There is an urgent unmet need to develop sensitive and specific biomarkers for the early detection of prostate cancer to reduce overtreatment and accompanying morbidity. We identified a group of differentially expressed long noncoding RNAs in prostate cancer cell lines and patient samples and further characterized six long noncoding RNAs (AK024556, XLOC_007697, LOC100287482, XLOC_005327, XLOC_008559, and XLOC_009911) in prostatic adenocarcinoma tissue samples (Gleason score >6.0) and compared them with matched normal (healthy) tissues. Interestingly, these markers were also successfully detected in patient urine samples and were found to be up-regulated when compared with normal (healthy) urine. AK024556 (SPRY4-IT1) was highly up-regulated in human prostate cancer cell line PC3 but not in LNCaP, and siRNA knockdown of SPRY4-IT1 in PC3 cells inhibited cell proliferation and invasion and increased cell apoptosis. Chromogenic in situ hybridization assay was developed to detect long noncoding RNAs in primary prostatic adenocarcinoma tissue samples, paving the way for clinical diagnostics. We believe that these results will set the stage for more extensive studies to develop novel long noncoding RNA-based diagnostic assays for early prostate cancer detection and will help to distinguish benign prostate cancer from precancerous lesions.The Journal of molecular diagnostics: JMD 10/2014; 16(6). DOI:10.1016/j.jmoldx.2014.06.009 · 3.48 Impact Factor