Urotensin II receptor on preoperative biopsy is associated with upstaging and upgrading in prostate cancer.
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ABSTRACT: Aim
A higher Gleason score was associated with a lower tumor urotensin II receptor (UTII-R) expression in prostate cancer patients.Methods
A retrospective review of formalin-fixed paraffin-embedded tumor tissue derived from those who had prostatectomy and matching biopsy specimens was conducted at six Institutions. UTII-R expression was evaluated on biopsy by immunohistochemistry.Results
A total of 58 subjects undergoing radical prostatectomy were included. At multivariate analysis, low UTII-R expression was a significant predictor of Gleason upgrading, with an odds ratio of 10.3 (95% CI: 1.55-68.4), and of pathology upstaging, with an odds ratio of 11.1 (95% CI: 1.23-100.48).Conclusions
UTII-R expression on biopsy was associated with Gleason upgrading and pathology upstaging in prostate cancer patients.
SUBMITTER: De Cobelli O
PROVIDER: S-EPMC5549758 | biostudies-literature | 2015 Nov
REPOSITORIES: biostudies-literature
Publications
Urotensin II receptor on preoperative biopsy is associated with upstaging and upgrading in prostate cancer.
De Cobelli Ottavio O Buonerba Carlo C Terracciano Daniela D Bottero Danilo D Lucarelli Giuseppe G Bove Pierluigi P Altieri Vincenzo V Coman Ioman I Perdonà Sisto S Facchini Gaetano G Berretta Massimiliano M Di Lorenzo Giuseppe G Grieco Paolo P Novellino Ettore E Franco Renato R Caraglia Michele M Manini Claudia C Mirone Vincenzo V De Placido Sabino S Sonpavde Guru G Ferro Matteo M
Future oncology (London, England) 20150918 22
<h4>Aim</h4>A higher Gleason score was associated with a lower tumor urotensin II receptor (UTII-R) expression in prostate cancer patients.<h4>Methods</h4>A retrospective review of formalin-fixed paraffin-embedded tumor tissue derived from those who had prostatectomy and matching biopsy specimens was conducted at six Institutions. UTII-R expression was evaluated on biopsy by immunohistochemistry.<h4>Results</h4>A total of 58 subjects undergoing radical prostatectomy were included. At multivariat ...[more]
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Project description:BackgroundSignificant numbers of prostate cancer (PCa) patients experience tumour upstaging and upgrading in surgical specimens that cause serious problems in timely and proper selection of the treatment strategy. This study was aimed at the evaluation of a set of established epigenetic biomarkers as a noninvasive tool for more accurate PCa categorization before radical prostatectomy (RP).MethodsQuantitative methylation-specific PCR was applied for the methylation analysis of RARB, RASSF1, and GSTP1 in 514 preoperatively collected voided or catheterized urine samples from the single-centre cohort of 1056 treatment-naïve PCa patients who underwent RP. The rates of biopsy upgrading and upstaging were analysed in the whole cohort.ResultsPathological examination of RP specimens revealed Gleason score upgrading in 27.2% and upstaging in 20.3% of the patients with a total misclassification rate of 39.0%. DNA methylation changes in at least one gene were detected in more than 80% of urine samples. Combination of the PSA test with the three-gene methylation analysis in urine was a significant predictor of pathological upstaging and upgrading (P < 0.050), however, with limited increase in overall accuracy. The PSA test or each gene alone was not informative enough.ConclusionsThe urinary DNA methylation assay in combination with serum PSA may predict tumour stage or grade migration post-RP aiding in improved individual risk assessment and appropriate treatment selection. Clinical utility of these biomarkers should be proven in larger multi-centre studies.
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Project description:Several studies suggest race-based health disparities in men with low-risk prostate cancer (PCa), with African American males having poorer oncological outcomes. We sought to determine the prevalence and predictors of pathological upgrading and upstaging in Jamaican men with low-risk PCa treated with radical prostatectomy (RP). Data on 141 men who met the National Comprehensive Cancer Network criteria for low-risk PCa and underwent RP at a single institution were reviewed. All men had a transrectal ultrasound-guided biopsy. Pre-operative clinical and final pathological data were obtained. Data were summarised as means and standard deviations or percentages as appropriate. Bivariate analyses such as independent samples t-tests and chi-square tables were conducted and logistic regression models were estimated to predict upgrading (>Gleason 6) and upstaging (p ? T3). The mean age was 59.5 ± 7.8 years with mean prostate specific antigen (PSA) of 6.6 ± 2 ng/mL. A total of 48.3% of men were upgraded and 11.4% were upstaged. Bivariate analyses indicated that PSA (p = 0.008) and percentage positive cores (p = 0.002) were associated with upgrading. PSA (p = 0.042) and percentage positive cores (p = 0.003) were significantly associated with upstaging. The odds of upgrading increased with increased PSA levels (OR 1.40, 95% CI 1.05-1.87, p = 0.021) or increased percentage positive cores (OR 8.27, 95% CI 2.19-31.16, p = 0.002). The odds of upstaging increased with increased PSA levels (OR 1.4, 95% CI 1.01-1.96, p = 0.046) and with increased percentages positive cores (OR 11.4; 95% CI 2.06-63.09, p = 0.005). Jamaican men with low-risk PCa are at high risk of pathological upgrading and upstaging at RP. These findings should be taken into consideration when discussing treatment options with these patients.
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Project description:When distinguishing between indolent and potentially harmful prostate cancers, the Gleason score is the most important variable, but may be inaccurate in biopsies due to tumor under-sampling. This study investigated whether a molecular feature, PTEN protein loss, could help identify which Gleason score 6 tumors on biopsy are likely to be upgraded at radical prostatectomy. Seventy one patients with Gleason score 6 tumors on biopsy upgraded to Gleason score 7 or higher at prostatectomy (cases) were compared with 103 patients with Gleason score 6 on both biopsy and prostatectomy (controls). A validated immunohistochemical assay for PTEN was performed, followed by fluorescence in situ hybridization (FISH) to detect PTEN gene deletion in a subset. PTEN protein loss and clinical-pathologic variables were assessed by logistic regression. Upgraded patients were older than controls (61.8 vs 59.3 years), had higher pre-operative PSA levels (6.5 vs 5.3 ng/ml) and a higher fraction of involved cores (0.42 vs 0.36). PTEN loss by immunohistochemistry was found in 18% (13/71) of upgraded cases compared with 7% (7/103) of controls (P=0.02). Comparison between PTEN immunohistochemistry and PTEN FISH showed the assays were highly concordant, with 97% (65/67) of evaluated biopsies with intact PTEN protein lacking PTEN gene deletion, and 81% (13/16) of the biopsies with PTEN protein loss showing homozygous PTEN gene deletion. Tumors with PTEN protein loss were more likely to be upgraded at radical prostatectomy than those without loss, even after adjusting for age, preoperative PSA, clinical stage and race (odds ratio=3.04 (1.08-8.55; P=0.035)). PTEN loss in Gleason score 6 biopsies identifies a subset of prostate tumors at increased risk of upgrading at radical prostatectomy. These data provide evidence that a genetic event can improve Gleason score accuracy and highlight a path toward the clinical use of molecular markers to augment pathologic grading.
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Project description:To investigate the impact of race on the risk of pathological upgrading and upstaging at radical prostatectomy (RP) in an Asian (Korean) and Western (Caucasian) cohort eligible for active surveillance (AS).We performed a retrospective cohort study of 854 patients eligible for AS who underwent RP in United States (n = 261) and Korea (n = 593) between 2006 and 2015. After adjusting for age, PSA level, and prostate volume, we utilized multivariate logistic regression analysis to assess the effect of race on upgrading or upstaging.There were significant differences between Caucasian and Korean patients in terms of age at surgery (60.2 yr. vs. 64.1 yr.), PSA density (0.115 ng/mL/mL vs. 0.165 ng/mL/mL) and mean number of positive cores (3.5 vs. 2.4), but not in preoperative PSA values (5.11 ng/mL vs. 5.05 ng/mL). The rate of upstaging from cT1 or cT2 to pT3 or higher was not significantly different between the two cohorts (8.8% vs. 11.0%, P = 0.341). However, there were higher rates of upgrading to high-grade cancer (Gleason 4+3 or higher) in Korean patients (9.1%) when compared to Caucasian counterparts (2.7%) (P = 0.003). Multivariate logistic regression analysis showed that age (OR 1.07, P < 0.001) and smaller prostate volume (OR 0.97, P < 0.001), but not race, were significantly associated with upstaging or upgrading.There were no differences in rates of upgrading or upstaging between Caucasian and Korean men eligible for active surveillance.
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Project description:ObjectivesTo determine if the presence of adverse pathological features in patients eligible for active surveillance (AS) are prognostic of poor oncological outcomes, independent of pretreatment risk.Patients and methodsA retrospective analysis was performed on patients who underwent radical prostatectomy (RP) at two institutions (Cleveland Clinic Foundation and Memorial Sloan Kettering Cancer Center) between 1987 and 2008, and who had subsequent follow-up. Rates of biochemical recurrence, metastasis and death from prostate cancer were compared amongst patients with adverse pathological features (Gleason score ≥7, ≥pT3, or lymph node invasion) based on D'Amico clinical risk (low vs intermediate/high). We also compared survival outcomes between patients with and without pathological upgrading/upstaging amongst D'Amico low-risk patients. Univariate and multivariable Cox regression models were used to assess the association between clinical risk, pathological reclassification, and oncological outcomes.ResultsWe identified 16 341 patients who underwent RP, of whom 6 371 were clinically low-risk. Adverse outcomes in men with adverse pathological features were significantly lower in those with low clinical risk, with an ~50% and ~70% reduction in the risk of metastasis and death, respectively. Only pathological upgrading/upstaging to Gleason score ≥8, seminal vesicle invasion, and lymph node invasion from clinical low-risk disease, were associated with adverse outcomes. However, these types of reclassification were rare.ConclusionClinical low-risk patients with pathological upgrading/upstaging have substantially lower rates of important oncological outcomes compared to those with higher pretreatment risk and not substantially different than low-risk patients without pathological upgrading/upstaging. These results call into question the use of this endpoint to counsel patients about the merits and risks of AS.
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Project description:BackgroundActive surveillance (AS) is increasingly accepted for managing low-risk prostate cancer, yet there is no consensus about implementation. This lack of consensus is due in part to uncertainty about risks for disease progression, which have not been systematically compared or integrated across AS studies with variable surveillance protocols and dropout to active treatment.ObjectiveTo compare risks for upgrading from a Gleason score (GS) of 6 or less to 7 or more across AS studies after accounting for differences in surveillance intervals and competing treatments and to evaluate tradeoffs of more versus less frequent biopsies.DesignJoint statistical model of longitudinal prostate-specific antigen (PSA) levels and risks for biopsy upgrading.SettingJohns Hopkins University (JHU); Canary Prostate Active Surveillance Study (PASS); University of California, San Francisco (UCSF); and University of Toronto (UT) AS studies.Patients2576 men aged 40 to 80 years with a GS between 2 and 6 and clinical stage T1 or T2 prostate cancer enrolled between 1995 and 2014.MeasurementsPSA levels and biopsy GSs.ResultsAfter variable surveillance intervals and competing treatments were accounted for, estimated risks for biopsy upgrading were similar in the PASS and UT studies but higher in UCSF and lower in JHU studies. All cohorts had a delay of 3 to 5 months in detecting upgrading with biennial biopsies starting after a first confirmatory biopsy versus annual biopsies.LimitationThe model does not account for possible misclassification of biopsy GS.ConclusionMen in different AS studies have different risks for biopsy upgrading after variable surveillance protocols and competing treatments are accounted for. Despite these differences, the consequences of more versus less frequent biopsies seem to be similar across cohorts. Biennial biopsies seem to be an acceptable alternative to annual biopsies.Primary funding sourceNational Cancer Institute.
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Project description:PurposeMultiparametric magnetic resonance imaging and fusion biopsy detect more high risk prostate cancer and less low risk prostate cancer than systematic biopsy. However, there remains a small subset of patients in whom systematic biopsy captures higher grade disease than fusion biopsy. We sought to identify potential mechanisms of the failure of fusion biopsy in the detection of clinically significant prostate cancer.Materials and methodsWe reviewed a prospectively maintained database of patients who underwent multiparametric magnetic resonance imaging followed by fusion biopsy and systematic biopsy from 2007 to 2014. In patients in whom disease was upgraded to clinically significant disease (Gleason 7 or greater) by systematic biopsy over fusion biopsy, independent re-review of magnetic resonance imaging, archived biopsy imaging and whole mount pathology as well as needle coordinate mapping were performed. Multivariate logistic regression analysis was done to determine predictors of upgrading by systematic biopsy.ResultsDisease was upgraded based on systematic biopsy over fusion biopsy in 135 of 1,003 patients (13.5%), of whom only 62 (6.2%) were upgraded to intermediate (Gleason 7) and high risk (Gleason 8 or greater) prostate cancer (51 or 5.1% and 11 or 1.1%, respectively). On multivariate analysis lower prostate specific antigen (p <0.001), higher magnetic resonance imaging prostate volume (p <0.001) and a lower number of target cores (p = 0.001) were predictors of upgrading by systematic biopsy. Main mechanisms of under grading by fusion biopsy included multiparametric magnetic resonance imaging reader oversight, presence of magnetic resonance imaging invisible cancer, fusion biopsy technique error and intralesion Gleason heterogeneity.ConclusionsMagnetic resonance imaging and fusion biopsy rarely missed clinically significant prostate cancer as only 62 of 1,003 cases (6.2%) were upgraded to clinically significant disease by systematic biopsy. Imaging and biopsy techniques are continually refined. Further studies will help clarify mechanisms of fusion biopsy failure and the patient populations that benefit from systematic biopsy in addition to fusion biopsy.
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Project description:BackgroundNon Muscle Invasive Bladder Transitional Cancer (NMIBC) and Muscle Invasive Bladder Transitional Cancer (MIBC)/invasive have different gene profile and clinical course. NMIBC prognosis is not completely predictable, since the relapse rate is higher than 20%, even in the form of MIBC. The aim of this study is to evaluate if UTR expression can discriminate between NMIBC and MIBC and predict the risk of relapses in NMIBCs.MethodsWe have investigated upon urotensin-II (UII) receptor (UTR) expression in vivo in 159 patients affected by NMIBC. The biological role of UTR was also investigated in vitro. UTR expression was evaluated in a tissue-micro-array, consisting of normal, NMIBC and invasive bTCC samples.ResultsUTR discriminated between NMIBC and MIBC and showed a significant correlation between low UTR expression and shorter disease free survival in NMIBC. The superagonist UPG84 induced growth suppression at nM concentrations on 3/4 cell lines. Bladder cancer cell treatment with the antagonist urantide or the knock-down of UTR with a specific shRNA significantly blocked both the motility and invasion of bladder cancer cells.ConclusionsThe evaluation of UTR expression can discriminate between NMIBC at high and low risk of relapse. Moreover, our data suggest that UTR is involved in the regulation of motility, invasion and proliferation of bladder cancer cells. High UTR expression is an independent prognostic factor of good prognosis for NMIBC regulating motility and invasion of bladder cancer cells.
| S-EPMC4061920 | biostudies-literature
Project description:An increase or 'upgrade' in Gleason Score (GS) in prostate cancer following Transrectal Ultrasound (TRUS) guided biopsies remains a significant challenge to overcome. to evaluate whether MRI has the potential to narrow the discrepancy of histopathological grades between biopsy and radical prostatectomy, three hundred and thirty men treated consecutively by laparoscopic radical prostatectomy (LRP) between July 2014 and January 2019 with localized prostate cancer were included in this study. Independent radiologists and pathologists assessed the MRI and histopathology of the biopsies and prostatectomy specimens respectively. A multivariate model was constructed using logistic regression analysis to assess the ability of MRI to predict upgrading in biopsy GS in a nomogram. A decision-analysis curve was constructed assessing impact of nomogram using different thresholds for probabilities of upgrading. PIRADS scores were obtained from MRI scans in all the included cases. In a multivariate analysis, the PIRADS v2.0 score significantly improved prediction ability of MRI scans for upgrading of biopsy GS (p?=?0.001, 95% CI [0.06-0.034]), which improved the C-index of predictive nomogram significantly (0.90 vs. 0.64, p?<?0.05). PIRADS v2.0 score was an independent predictor of postoperative GS upgrading and this should be taken into consideration while offering treatment options to men with localized prostate cancer.
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