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.
"The PCA3 assay, in particular, has a high sensitivity for prostate cancer detection, whereas the TMPRSS2-ERG fusion, which is present in approximately 50% of tumors , has a very high specificity for prostate cancer. We envision that a SChLAP1-based assay (i.e., ISH) could complement these tests because neither PCA3 nor TMPRSS2-ERG has been shown as a definitive strong prognostic early-stage biomarker    . Thus, although SChLAP1 has a poor sensitivity for cancer overall, its utility as a strong prognostic test "
[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 · 4.25 Impact Factor
"The increased specificity is contrasted by a reduced sensitivity and PCA3 is therefore applied in association with PSA where it can reduce the number of unnecessary biopsies after a negative biopsy in men with elevated PSA levels [18, 19]. PCA3 may also have some prognostic potential inasmuch as its expression correlates with the Gleason score [20, 21], yet it has not been reported whether the combination of PCA3 and Gleason can improve prognostic power. "
[Show abstract][Hide abstract] ABSTRACT: Biomarkers are important for early detection of cancer, prognosis, response prediction, and detection of residual or relapsing disease. Special attention has been given to diagnostic markers for prostate cancer since it is thought that early detection and surgery might reduce prostate cancer-specific mortality. The use of prostate-specific antigen, PSA (KLK3), has been debated on the base of cohort studies that show that its use in preventive screenings only marginally influences mortality from prostate cancer. Many groups have identified alternative or additional markers, among which PCA3, in order to detect early prostate cancer through screening, to distinguish potentially lethal from indolent prostate cancers, and to guide the treatment decision. The large number of markers proposed has led us to the present study in which we analyze these indicators for their diagnostic and prognostic potential using publicly available genomic data. We identified 380 markers from literature analysis on 20,000 articles on prostate cancer markers. The most interesting ones appeared to be claudin 3 (CLDN3) and alpha-methysacyl-CoA racemase highly expressed in prostate cancer and filamin C (FLNC) and keratin 5 with highest expression in normal prostate tissue. None of the markers proposed can compete with PSA for tissue specificity. The indicators proposed generally show a great variability of expression in normal and tumor tissue or are expressed at similar levels in other tissues. Those proposed as prognostic markers distinguish cases with marginally different risk of progression and appear to have a clinically limited use. We used data sets sampling 152 prostate tissues, data sets with 281 prostate cancers analyzed by microarray analysis and a study of integrated genomics on 218 cases to develop a multigene score. A multivariate model that combines several indicators increases the discrimination power but does not add impressively to the information obtained from Gleason scoring. This analysis of 10 years of marker research suggests that diagnostic and prognostic testing is more difficult in prostate cancer than in other neoplasms and that we must continue to search for better candidates.
Electronic supplementary material
The online version of this article (doi:10.1007/s10555-013-9470-4) contains supplementary material, which is available to authorized users.
CANCER AND METASTASIS REVIEW 01/2014; 33(2-3). DOI:10.1007/s10555-013-9470-4 · 7.23 Impact Factor
"While Whitman  did not find a significant association with prostatectomy Gleason score, their study showed that PCA3 was an independent predictor of ECE. They also showed that PCA3 combined synergistically with serum PSA and biopsy Gleason score to greatly improve ECE predictive ability . A more recent study did not find the same correlations with PCA3; however, the study used post-DRE urine sediments instead of whole urine and cannot be directly compared . "
[Show abstract][Hide abstract] ABSTRACT: Prostate cancer is the second leading cause of cancer deaths in men in the United States. Use of the serum prostate specific antigen (PSA) test to screen men for prostate cancer since the late 1980s has improved the early detection of prostate cancer, however low specificity of the test translates to numerous false positive results and many unnecessary biopsies. New biomarkers to aid in prostate cancer diagnosis are emerging and prostate cancer gene 3 (PCA3) is one such marker. PCA3 is a noncoding RNA that is highly over-expressed in prostate cancer tissue compared to benign tissue. A non-invasive test for PCA3 was developed using whole urine collected after a digital rectal exam (DRE). Numerous clinical studies have demonstrated the utility of PCA3 for the diagnosis of prostate cancer and some studies suggest that PCA3 may also have prognostic value. The use of PCA3 in combination with serum PSA and other clinical information enhances the diagnostic accuracy of prostate cancer detection and will enable physicians to make more informed decisions with patients at risk for prostate cancer.
Cancer letters 02/2011; 301(1):1-6. DOI:10.1016/j.canlet.2010.10.019 · 5.62 Impact Factor
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