共查询到20条相似文献,搜索用时 31 毫秒
1.
Joost L. Boormans Karin G. Hermans Angelique C.J. Ziel-van der Made Geert J.H.L. van Leenders Mark F. Wildhagen Laurence Collette Fritz H. Schröder Jan Trapman Paul C.M.S. Verhagen 《European urology》2010
Background
Fusion of the androgen-regulated gene transmembrane protease, serine 2, TMPRSS2, to the v-ets erythroblastosis virus E26 oncogene homolog (avian), ERG, of the erythroblast transformation-specific (ETS) family is the most common genetic alteration in prostate cancer (PCa).Objective
To determine whether expression of androgen-regulated TMPRSS2-ERG predicts response to endocrine treatment in hormone-naïve, node-positive PCa.Design, setting, and participants
Eighty-five patients with histologically confirmed, node-positive PCa who were without treatment at the moment of lymph node dissection were analysed. RNA was isolated from the paraffin-embedded lymph node metastases and complementary DNA (cDNA) was made. The quality of cDNA was tested by polymerase chain reaction (PCR) analysis of the expression of the housekeeping gene hydroxymethylbilane synthase, HMBS (formerly PBGD). TMPRSS2-ERG expression was analysed by PCR using a forward primer in TMPRSS2 exon 1 and a reverse primer in ERG exon 4.Measurements
The primary end point was time from start of endocrine therapy to the occurrence of three consecutive rises in prostate-specific antigen (PSA) that were at least 2 wk apart and resulted in two 50% increases over the PSA nadir. Secondary end points were time to PSA nadir after start of endocrine treatment and cancer-specific and overall survival.Results and limitations
TMPRSS2-ERG was expressed in 59% of the 71 patients who could be analysed. Median duration of response to endocrine therapy was 20.9 mo versus 24.1 mo for gene fusion–positive versus gene fusion–negative patients (95% confidence intervals: 18.6–23.1 vs 18.9–29.4, p = 0.70). Furthermore, no significant differences were seen between the two groups for the secondary end points.Conclusions
Expression of TMPRSS2-ERG is frequent in lymph node metastases of patients with untreated PCa; however, expression of this androgen-regulated fusion gene did not correspond with duration of response to endocrine therapy. Our results suggest that expression of TMPRSS2-ERG is not a candidate marker to select for metastatic PCa patients who will benefit more from endocrine treatment. 相似文献2.
Gisele H.J.M. Leyten Daphne Hessels Sander A. Jannink Frank P. Smit Hans de Jong Erik B. Cornel Theo M. de Reijke Henk Vergunst Paul Kil Ben C. Knipscheer Inge M. van Oort Peter F.A. Mulders Christina A. Hulsbergen-van de Kaa Jack A. Schalken 《European urology》2014
Background
Prostate cancer antigen 3 (PCA3) and v-ets erythroblastosis virus E26 oncogene homolog (TMPRSS2-ERG) gene fusions are promising prostate cancer (PCa) specific biomarkers that can be measured in urine.Objective
To evaluate the diagnostic and prognostic value of Progensa PCA3 and TMPRSS2-ERG gene fusions (as individual biomarkers and as a panel) for PCa in a prospective multicentre setting.Design, setting, and participants
At six centres, post–digital rectal examination first-catch urine specimens prior to prostate biopsies were prospectively collected from 497 men. We assessed the predictive value of Progensa PCA3 and TMPRSS2-ERG (quantitative nucleic acid amplification assay to detect TMPRSS2-ERG messenger RNA [mRNA]) for PCa, Gleason score, clinical tumour stage, and PCa significance (individually and as a marker panel). This was compared with serum prostate-specific antigen and the European Randomised Study of Screening for Prostate Cancer (ERSPC) risk calculator. In a subgroup (n = 61) we evaluated biomarker association with prostatectomy outcome.Outcome measurements and statistical analysis
Univariate and multivariate logistic regression analysis and receiver operating curves were used.Results and limitations
Urine samples of 443 men contained sufficient mRNA for marker analysis. PCa was diagnosed in 196 of 443 men. Both PCA3 and TMPRSS2-ERG had significant additional predictive value to the ERSPC risk calculator parameters in multivariate analysis (p < 0.001 and resp. p = 0.002). The area under the curve (AUC) increased from 0.799 (ERSPC risk calculator), to 0.833 (ERSPC risk calculator plus PCA3), to 0.842 (ERSPC risk calculator plus PCA3 plus TMPRSS2-ERG) to predict PCa. Sensitivity of PCA3 increased from 68% to 76% when combined with TMPRSS2-ERG. TMPRSS2-ERG added significant predictive value to the ERSPC risk calculator to predict biopsy Gleason score (p < 0.001) and clinical tumour stage (p = 0.023), whereas PCA3 did not.Conclusions
TMPRSS2-ERG had independent additional predictive value to PCA3 and the ERSPC risk calculator parameters for predicting PCa. TMPRSS2-ERG had prognostic value, whereas PCA3 did not. Implementing the novel urinary biomarker panel PCA3 and TMPRSS2-ERG into clinical practice would lead to a considerable reduction of the number of prostate biopsies. 相似文献3.
Background
Our group has previously shown that prostate-specific antigen (PSA) velocity (PSAV) is associated with the presence of life-threatening prostate cancer. Less is known about the relative utility of pretreatment PSA doubling time (PSA DT) to predict tumor aggressiveness.Objective
To compare the utility of PSAV and PSA DT for the prediction of life-threatening prostate cancer.Design, setting, and participants
From the Baltimore Longitudinal Study of Aging, we identified 681 men with serial PSA measurements.Measurements
Receiver operating characteristic analysis was used to evaluate the relationship between PSAV, PSA DT, and the presence of high-risk disease.Results and limitations
Within the period of 5 yr prior to diagnosis, PSAV was significantly higher among men with high-risk or fatal prostate cancer than men without it. By contrast, PSA DT was not significantly associated with high-risk or fatal disease. On multivariate analysis, including age, date of diagnosis, and PSA, the addition of PSAV significantly improved the concordance index from 0.85 to 0.88 (p < 0.001), whereas PSA DT did not.Conclusions
These data suggest that PSAV is more useful than PSA DT in the pretreatment setting to help identify those men with life-threatening disease. 相似文献4.
Daniel E. Spratt Chi Zhang Zachary S. Zumsteg Xin Pei Zhigang Zhang Michael J. Zelefsky 《European urology》2013
Background
In vitro data and early clinical results suggest that metformin has desirable antineoplastic effects and has a theoretical benefit on castration-resistant prostate cancer (CRPC).Objective
To determine whether the use of metformin would be associated with improved clinical outcomes and a reduction in the development of CRPC.Design, setting, and participants
Data from 2901 consecutive patients (157 metformin, 162 diabetic non-metformin, and 2582 nondiabetic) with localized prostate cancer treated with external-beam radiation therapy from 1992 to 2008 were collected from a single institution in the United States.Intervention
Use of metformin in localized prostate cancer.Outcome measurements and statistical analysis
Univariate and multivariate regression models utilizing k-sample, Fine and Gray, Cox regression, log-rank, and Kaplan-Meier methods to assess prostate-specific antigen-recurrence-free survival (PSA-RFS), distant metastases-free survival (DMFS), prostate cancer–specific mortality (PCSM), overall survival (OS), and development of CRPC.Results and limitations
With a median follow-up of 8.7 yr, the 10-yr actuarial rates for metformin, diabetic non-metformin, and nondiabetic patients for PCSM were 2.7%, 21.9%, and 8.2% (log-rank p ≤ 0.001), respectively. Metformin use independently predicted (correcting for PSA, T stage, Gleason score, age, diabetic status, and androgen-deprivation therapy use) improvement in all outcomes compared with the diabetic non-metformin group; PSA-RFS (hazard ratio [HR]: 1.99 [1.24–3.18]; p = 0.004), DMFS (adjusted HR: 3.68 [1.78–7.62]; p < 0.001), and PCSM (HR: 5.15 [1.53–17.35]; p = 0.008). Metformin use was also independently associated with a decrease in the development of CRPC in patients experiencing biochemical failure compared with diabetic non-metformin patients (odds ratio: 14.81 [1.83–119.89]; p = 0.01). The retrospective study design was the primary limitation of the study.Conclusions
To our knowledge, our results are the first clinical data to indicate that metformin use may improve PSA-RFS, DMFS, PCSM, OS, and reduce the development of CRPC in prostate cancer patients. Further validation of metformin's potential benefits is warranted. 相似文献5.
Nguyen PN Violette P Chan S Tanguay S Kassouf W Aprikian A Chen JZ 《European urology》2011,59(3):407-414
Background
The TMPRSS2:ERG fusion is both prevalent and unique to prostate cancer (PCa) and has great potential for noninvasive diagnosis of PCa in bodily fluids.Objectives
To evaluate the specificity and sensitivity of the TMPRSS2:ERG fusion in urine from diverse clinical contexts and to explore potential clinical applications.Design, setting, and participants
A total of 101 subjects were enrolled in 2008 from urologic oncology clinics to form three study groups: 44 PCa free, 46 confirmed PCa, and 11 negative prostate biopsies. The PCa-free group included females, healthy young men, and post–radical prostatectomy (RP) patients. The confirmed PCa group was composed of patients under active surveillance, scheduled for treatment, or with metastatic disease.Measurements
Urine was collected after attentive digital rectal exam (DRE) and coded to blind group allocation for laboratory test. RNA from urine sediments was analyzed using a panel of four TMPRSS2:ERG fusion markers with quantitative polymerase chain reaction (qPCR).Results and limitations
Our fusion markers demonstrated very high technical specificity and sensitivity for detecting a single fusion-positive cancer cell (VCaP) in the presence of at least 3000 cells in urine sediments. In clinical analysis, there were no fusion-positive samples in the PCa-free group (0 of 44 samples), while there were 16 of 46 (34.8%) fusion-positive samples in the confirmed PCa group. The fusion incidence varied significantly among the three PCa subgroups. The clinical sensitivity increased to 45.4% in cancer patients prior to treatments. The fusion markers were detected in 2 of 11 (18.2%) biopsy-negative patients, suggesting potentially false negative biopsies. This study is not prospective and is limited in sample sizes.Conclusions
Our novel panel of TMPRSS2:ERG fusion markers provided a very specific and sensitive tool for urine-based detection of PCa. Theses markers can potentially be used to diagnose patients with PCa who have negative biopsies. 相似文献6.
Delila Gasi Tandefelt Joost L. Boormans Hetty A. van der Korput Guido W. Jenster Jan Trapman 《European urology》2013
Background
The molecular basis of the clinical heterogeneity of prostate cancer (PCa) is not well understood.Objective
The purpose of our study was to identify and characterize genes in a clinically relevant gene expression signature in a subgroup of primary PCa positive for transmembrane protease, serine 2 (TMPRSS2)–v-ets erythroblastosis virus E26 oncogene homolog (avian) (ERG).Design, setting, and participants
We studied gene expression profiles by unsupervised hierarchical clustering in 48 primary PCas from patients with a long clinical follow-up. Results were correlated with clinical outcome and validated in an independent patient cohort. Selected genes from a defined classifier were tested in vitro for biologic properties.Intervention
Initial treatment of primary tumors was radical prostatectomy.Outcome measurements and statistical analysis
Associations between clinical and histopathologic variables were evaluated by the Pearson χ2 test, Mann-Whitney U test, or Kruskal-Wallis test, where appropriate. The log-rank test or Breslow method was used for statistical analysis of Kaplan-Meier survival curves.Results and limitations
Most tumors that overexpressed ERG clustered separately from other primary PCas. No differences in any clinical end points between ERG-positive and ERG-negative cancers were detected. Importantly, within the ERG-positive samples, two subgroups were identified, which differed significantly in prostate-specific antigen recurrence-free survival, and cancer-specific and overall survival. From our findings, we defined a gene expression classifier of 36 genes. In a second, completely independent tumor set, the classifier also distinguished ERG-positive subgroups with different clinical outcome. In both patient cohorts, the classifier was not predictive in ERG-negative tumors. Biologic processes regulated by genes in the classifier included cell adhesion and bone remodeling. Tumor growth factor-β signaling was indicated as the main differing signaling pathway between the two ERG subgroups. In vitro biologic assays of two selected genes from the classifier (inhibin, beta A [INHBA] and cadherin 11, type 2, OB-cadherin (osteoblast) [CDH11]) supported a functional role in PCa progression. Possible multifocality and limited number of PCa samples can be limitations of the study.Conclusions
The classifier identified can contribute to prediction of tumor progression in ERG-positive primary prostate tumors and might be instrumental in therapy decisions. 相似文献7.
Robert Karlsson Markus Aly Mark Clements Lilly Zheng Jan Adolfsson Jianfeng Xu Henrik Grönberg Fredrik Wiklund 《European urology》2014
Background
A rare but recurrent missense mutation (G84E, rs138213197) in the gene homeobox B13 (HOXB13) was recently reported to be associated with hereditary prostate cancer.Objective
To explore the prevalence and penetrance of HOXB13 G84E in a general population.Design, setting, and participants
G84E and 14 additional HOXB13 polymorphisms were genotyped in two population-based, Swedish, case-control samples (Cancer of the Prostate in Sweden [CAPS] and Stockholm-1) comprising 4693 controls and 5003 prostate cancer cases. CAPS collected data on patients and population controls nationally between 2001 and 2003. Stockholm-1 collected data on biopsy-positive patients and biopsy-negative controls in the Stockholm area between 2005 and 2007.Outcome measurements and statistical analysis
The outcome was pathologically verified prostate cancer. Relative and absolute risks among HOXB13 G84E mutation carriers were explored, as was the combined impact on disease risk of G84E and a polygenic score based on 33 established, common, low-risk variants.Results and limitations
HOXB13 G84E was observed in 1.3% of population controls and was strongly associated with prostate cancer risk (CAPS: odds ratio [OR]: 3.4; 95% confidence interval [CI], 2.2–5.4; Stockholm-1: OR: 3.5; 95% CI, 2.4–5.2). The strongest association was observed for young-onset (OR: 8.6; 95% CI, 5.1–14.0) and hereditary (OR: 6.6; 95% CI, 3.3–12.0) prostate cancer. Haplotype analyses supported that G84E is a founder mutation. G84E carriers have an estimated 33% (95% CI, 23–46) cumulative risk to age 80 yr of prostate cancer, compared to 12% (95% CI, 11–13) among noncarriers. For G84E carriers within the top quartile of a polygenic score of established susceptibility variants, the cumulative risk was estimated at 48% (95% CI, 36–64).Conclusions
HOXB13 G84E is prevalent in >1% of the Swedish population and is associated with a 3.5-fold increased risk of prostate cancer. One-third of G84E carriers will be diagnosed with prostate cancer, which has implications for surveillance in mutation carriers. 相似文献8.
Christopher J. Weight Simon P. Kim Debra J. Jacobson Michaela E. McGree Stephen A. Boorjian R. Houston Thompson Bradley C. Leibovich R. Jeffrey Karnes Jennifer St. Sauver 《European urology》2013
Background
Lower urinary tract symptoms (LUTS) are common and have been associated with the subsequent diagnosis of prostate cancer (PCa) in population cohorts.Objective
To determine whether the association between LUTS and PCa is due to the intensity of PCa testing after LUTS diagnosis.Design, setting, and participants
We prospectively followed a representative, population-based cohort of 1922 men, aged 40–79 yr, from 1990 until 2010 with interviews, questionnaires, and abstracting of medical records for prostate outcomes. Men were excluded if they had a previous prostate biopsy or PCa diagnosis. Self-reported LUTS was defined as an American Urological Association symptom index score >7 (n = 621). Men treated for LUTS (n = 168) were identified from review of medical records and/or self report. Median follow-up was 11.8 yr (interquartile range: 10.7–12.3).Outcome measurements and statistical analysis
Associations between self-reported LUTS, or treatment for LUTS, and risk of subsequent prostate biopsy and PCa were estimated using Cox proportional hazard models.Results and limitations
Fifty-five percent of eligible men enrolled in the study. Men treated for LUTS were more likely to undergo a prostate biopsy (hazard ratio [HR]: 2.4; 95% confidence interval [CI], 1.7–3.3). Men younger than 65 yr who were treated for LUTS were more likely to be diagnosed with PCa (HR: 2.3, 95% CI, 1.5–3.5), while men aged >65 yr were not (HR: 0.89, 95% CI, 0.35–1.9). Men with self-reported LUTS were not more likely to be biopsied or diagnosed with PCa. Neither definition of LUTS was associated with subsequent intermediate- to high-risk cancer. The study is limited by lack of histologic or prostate-specific antigen level data for the cohort.Conclusions
These results indicate that a possible cause of the association between LUTS and PCa is increased diagnostic intensity among men whose LUTS come to the attention of physicians. Increased symptoms themselves were not associated with intensity of testing or diagnosis. 相似文献9.
Context
It is now possible to reduce a man's risk of developing biopsy-detectable prostate cancer. This review addresses the evidence and issues surrounding prostate cancer risk reduction.Objective
The scientific basis, therapeutic approach, and risks and benefits of prostate cancer prevention are reviewed. Special attention is given to data on 5α-reductase inhibitors (5-ARIs).Evidence acquisition
Medline searches consisted of articles published since 2003 regarding prostate cancer chemoprevention, prevention, or risk reduction, as well as searches around specific topics within this review.Evidence synthesis
Current data support the use of finasteride for prostate cancer risk reduction in appropriately selected men. The initial concern that finasteride increased the incidence of high-grade prostate cancer has not been confirmed by subsequent analyses. The efficacy of dutasteride, a dual 5-ARI, for prostate cancer risk reduction is currently being evaluated in men with elevated prostate-specific antigen (PSA). Other medical approaches to prostate cancer risk reduction, including statins, cyclooxygenase-2 (COX-2) inhibitors, selective estrogen receptor modulators, and dietary supplements, await validation in controlled clinical trials.Conclusions
It is now possible to reduce an individual man's risk of developing biopsy-detectable prostate cancer. The greatest benefit arises from decreasing the amount of unnecessary treatment in men harboring low-risk cancers. Presently, there is no evidence that 5-ARIs or any other approach to prostate cancer risk reduction will reduce the risk of lethal prostate cancers. Finasteride, however, does enhance the utility of PSA for diagnosing high-grade cancers. 相似文献10.
Context
Oestrogens were proven effective in the hormonal treatment of advanced prostate cancer (PCa) >60 yr ago and are still used as second-line hormonal therapy. Paradoxically, oestrogens might also be involved in the development and progression of PCa.Objective
To examine mechanisms of how oestrogens may affect prostate carcinogenesis and tumour progression.Evidence acquisition
Recent data obtained from animal, experimental, and clinical studies were reviewed.Evidence synthesis
The human prostate is equipped with a dual system of oestrogen receptors (oestrogen receptor alpha [ERα], oestrogen receptor beta [ERβ]) that undergoes profound remodelling during PCa development and tumour progression. In high-grade prostatic intraepithelial neoplasia (HGPIN), the ERα is upregulated and most likely mediates carcinogenic effects of estradiol as demonstrated in animal models. Preliminary clinical studies with the ERα antagonist toremifene have identified the ERα as a promising target for PCa prevention. The partial loss of the ERβ in HGPIN indicates that the ERβ acts as a tumour suppressor. The ERβ is generally retained in hormone-naïve PCa but is partially lost in castration-resistant disease. The progressive emergence of the ERα and the oestrogen-regulated progesterone receptor (PR) during PCa progression and hormone-refractory disease suggests that these tumours can use oestrogens and progestins for their growth. The TMPRSS2-ERG gene fusion recently reported as a potentially aggressive molecular subtype of PCa is regulated by ER-dependent signalling. TMPRSS2-ERG expression has been found to be increased by ERα agonist (oestrogens) and decreased by ERβ agonists.Conclusions
Oestrogens and their receptors are implicated in PCa development and tumour progression. There is significant potential for the use of ERα antagonists and ERβ agonists to prevent PCa and delay disease progression. Tumours equipped with the pertinent receptors are potential candidates for this new therapeutic approach. 相似文献11.
12.
Jansson KF Akre O Garmo H Bill-Axelson A Adolfsson J Stattin P Bratt O 《European urology》2012,62(4):656-661
Background
Genetic factors seem to be of greater importance in prostate cancer than in other forms of cancer. Studies have suggested familial concordance in survival, but the extent to which that is due to tumor characteristics is not known.Objective
We hypothesized that a brother of an index case with prostate cancer is at particularly increased risk of prostate cancer with the same tumor differentiation as the index case.Design, setting and participants
We identified 21 930 brothers of index cases with prostate cancer in the Prostate Cancer Data Base Sweden and followed them up for incidence of prostate cancer.Outcome measurements and statistical analysis
The relative risk of Gleason score–specific prostate cancer in the cohort of brothers was estimated by using the standardized incidence ratio (SIR) stratified by Gleason score of the index case. We estimated 95% confidence intervals (CIs) assuming a Poisson distribution.Results and limitations
Among brothers of index cases with Gleason score 8–10 cancer, the SIR was 2.53 (95% CI, 1.97–3.21) for a Gleason score 2–6 cancer and 4.00 (95% CI, 2.63–5.82) for a Gleason score 8–10 cancer. SIR for Gleason score 2–6 cancer among brothers decreased with time since the date of the index cases’ diagnoses, whereas the risk of Gleason 8–10 cancer increased over time for brothers of index cases with Gleason 8–10 cancer (p for trend = 0.009).Conclusions
Brothers of men with high-grade prostate cancer are at particularly increased risk of high-grade prostate cancer. Likewise, there is a concordance of less malignant prostate cancers within families. These findings may have direct clinical relevance for counseling men with a family history of prostate cancer. 相似文献13.
Giovanni Lughezzani Massimo Lazzeri Alexander Haese Thomas McNicholas Alexandre de la Taille Nicolò Maria Buffi Nicola Fossati Giuliana Lista Alessandro Larcher Alberto Abrate Alessandro Mistretta Vittorio Bini Joan Palou Redorta Markus Graefen Giorgio Guazzoni 《European urology》2014
Background
External validation of a prediction tool is mandatory to assess the tool's accuracy and generalizability within different patient cohorts.Objective
To externally validate a previously developed Prostate Health Index (PHI)–based nomogram for predicting the presence of prostate cancer (PCa) at biopsy.Design, setting, and participants
The study population consisted of 883 patients who were scheduled for a prostate biopsy at one of five European tertiary care centers. Total prostate-specific antigen (tPSA), free prostate-specific antigen (fPSA), and [−2]pro–prostate-specific antigen (p2PSA) levels were determined. The fPSA-to-tPSA ratio (%fPSA), p2PSA, and PHI ([p2PSA / fPSA] × √tPSA) were calculated.Intervention
Extended initial and repeat prostate biopsy.Outcome measurements and statistical analysis
Logistic regression models were fitted to test the predictors of PCa and to determine their predictive accuracy. A calibration plot was used to evaluate the extent of overestimation or underestimation between nomogram predictions and observed PCa rate. Decision curve analysis (DCA) provided an estimate of the net benefit obtained by using the PHI-based nomogram.Results and limitations
Of 833 patients, 365 (41.3%) were diagnosed with PCa at extended prostate biopsy. In accuracy analyses, PHI was the most informative predictor of PCa (0.68), outperforming tPSA (0.51) and %fPSA (0.64). The predictive accuracy of the previously developed nomogram was 75.2% (95% confidence interval, 71.4–78.1). Calibration of the nomogram was good in patients at a low to intermediate predicted probability of PCa, while calibration was suboptimal, with a tendency to overestimate the presence of PCa, in high-risk patients. Finally, DCA demonstrated that the use of the PHI-based nomogram resulted in the highest net benefit. The main limitation of the study is the fact that only Caucasian patients were included.Conclusions
At external validation, the previously developed PHI-based nomogram confirmed its ability to determine the presence of PCa at biopsy. These findings provide further evidence supporting the potential role of the nomogram in the biopsy decision pathway for European men with suspected PCa.Patient summary
In the current study, we externally validated a Prostate Health Index–based nomogram to predict the presence of prostate cancer (PCa) at biopsy. This tool may help clinicians determine the need for a prostate biopsy in European patients with suspected PCa. 相似文献14.
Line Victoria Moen Håkon Ramberg Sen Zhao Helene Hartvedt Grytli Anita Sveen Viktor Berge Rolf I. Skotheim Kristin Austlid Taskén Bjørn Steen Skålhegg 《Urologic oncology》2017,35(3):111.e1-111.e8
Background
Today overtreatment of indolent prostate cancers and undertreatment of aggressive prostate cancer are a major concern for patients, their families, and the health care system. New biomarkers distinguishing indolent and aggressive prostate cancer are needed to improve precision medicine. In prostate cancer, protein kinase A (PKA) is known to activate the androgen receptor and published data indicate that PKA subunits can act as predictive markers for response to radiation and chemotherapy. We have previously shown that the catalytic subunit, Cβ2, of PKA is up-regulated in prostate cancer and we would in this study investigate the potential of Cβ2 to become a prognostic biomarker in prostate cancer.Methods
Data were sampled from a total of 241 patients from 3 independent cohorts. We measured and compared Cβ2 messenger RNA (mRNA) levels in prostate tumor and nontumor samples (n = 22), and exon levels in a cohort of 50 tumor samples, as well as acquiring mRNA data from the publicly available database The cancer genome atlas (n = 169).Results
Cβ2 mRNA was up-regulated in prostate cancer in all 3 cohorts, measured by 3 different methods. Furthermore, the relative Cβ2 mRNA expression levels were lower in prostate cancer samples with Gleason score 8 to 10 compared with samples with Gleason score<8 (P = 0.004). Finally, low expression of Cβ2 mRNA in prostate cancer biopsies correlated with poor survival (hazard ratio = 0.20; 95% CI: 0.048–0.86; P = 0.031), adjusted for risk group and age.Conclusions
We suggest that Cβ2 mRNA expression may be used as a biomarker together with established prognostic markers to more precisely predict aggressiveness in patients diagnosed with prostate cancer. 相似文献15.
Marco Auprich Alexander Haese Jochen Walz Karl Pummer Alexandre de la Taille Markus Graefen Theo de Reijke Margit Fisch Paul Kil Paolo Gontero Jacques Irani Felix K.-H. Chun 《European urology》2010
Background
Prior to safely adopting risk stratification tools, their performance must be tested in an external patient cohort.Objective
To assess accuracy and generalizability of previously reported, internally validated, prebiopsy prostate cancer antigen 3 (PCA3) gene-based nomograms when applied to a large, external, European cohort of men at risk of prostate cancer (PCa).Design, setting, and participants
Biopsy data, including urinary PCA3 score, were available for 621 men at risk of PCa who were participating in a European multi-institutional study.Intervention
All patients underwent a ≥10-core prostate biopsy. Biopsy indication was based on suspicious digital rectal examination, persistently elevated prostate-specific antigen level (2.5–10 ng/ml) and/or suspicious histology (atypical small acinar proliferation of the prostate, >/= two cores affected by high-grade prostatic intraepithelial neoplasia in first set of biopsies).Measurements
PCA3 scores were assessed using the Progensa assay (Gen-Probe Inc, San Diego, CA, USA). According to the previously reported nomograms, different PCA3 score codings were used. The probability of a positive biopsy was calculated using previously published logistic regression coefficients. Predicted outcomes were compared to the actual biopsy results. Accuracy was calculated using the area under the curve as a measure of discrimination; calibration was explored graphically.Results and limitations
Biopsy-confirmed PCa was detected in 255 (41.1%) men. Median PCA3 score of biopsy-negative versus biopsy-positive men was 20 versus 48 in the total cohort, 17 versus 47 at initial biopsy, and 37 versus 53 at repeat biopsy (all p ≤ 0.002). External validation of all four previously reported PCA3-based nomograms demonstrated equally high accuracy (0.73–0.75) and excellent calibration. The main limitations of the study reside in its early detection setting, referral scenario, and participation of only tertiary-care centers.Conclusions
In accordance with the original publication, previously developed PCA3-based nomograms achieved high accuracy and sufficient calibration. These novel nomograms represent robust tools and are thus generalizable to European men at risk of harboring PCa. Consequently, in presence of a PCA3 score, these nomograms may be safely used to assist clinicians when prostate biopsy is contemplated. 相似文献16.
Karim Touijer Fernando P. Secin Angel M. Cronin Darren Katz Fernando Bianco Kinjal Vora Victor Reuter Andrew J. Vickers Bertrand Guillonneau 《European urology》2009
Background
While the published short-term oncologic outcomes after laparoscopic radical prostatectomy (LRP) are encouraging, intermediate and long-term data are lacking.Objective
We analyzed the oncologic outcome after LRP based on 10 yr of experience.Design, setting, and participants
This retrospective analysis of data prospectively collected from 1998 to 2007 studies 1564 consecutive patients with clinically localized prostate cancer (cT1c–cT3a) who underwent LRP.Intervention
LRP was performed by two surgeons at either L’Institut Mutualiste Montsouris (IMM) in Paris, France, or Memorial Sloan-Kettering Cancer Center (MSKCC) in New York City, USA.Measurements
Progression of disease was defined as a prostate-specific antigen (PSA) of ≥0.1 ng/ml with confirmatory rise or initiation of secondary therapy. Patients were stratified as low, intermediate, or high risk based on the pretreatment prostate cancer nomogram progression-free probability of >90%, 89–71%, and <70%, respectively.Results and limitations
The overall 5-yr and 8-yr probability of freedom from progression (PFP) was 78% (95% confidence interval [CI], 74–82%) and 71% (95% CI, 63–78%), respectively. For low-, intermediate-, and high-risk cancer, the 5-yr PFP was 91% (95% CI, 85–95%), 77% (95% CI, 71–82%), and 53% (95% CI, 40–65%), respectively. Surgical margins (SMs) were positive in 13% of the cases. Nodal metastases were detected in 3% of the patients after limited pelvic lymph node dissection (PLND) and in 10% after a standard PLND (p < 0.001). The 3-yr PFP for node-positive patients was 49%. There were 22 overall deaths and 2 deaths from prostate cancer.Conclusions
LRP provided 5- and 8-yr cancer control in 78% and 71% of patients, respectively, with clinically localized prostate cancer and in 53% of those with high-risk cancer at 5 yr. A PLND limited to the external iliac nodal group is inadequate for detecting nodal metastases. 相似文献17.
Shaw G Price AM Ktori E Bisson I Purkis PE McFaul S Oliver RT Prowse DM 《European urology》2008,54(6):1333-1343
Objectives
Androgen-deprivation therapy effectively shrinks hormone-naïve prostate cancer, both in the prostate and at sites of distant metastasis. However prolonged androgen deprivation generally results in relapse and androgen-independent tumour growth, which is inevitably fatal. The molecular events that enable prostate cancer cells to proliferate in reduced androgen conditions are poorly understood. Here we investigate the role of Hedgehog signalling in androgen-independent prostate cancer (AIPC).Methods
Activity of the Hedgehog signalling pathway was analysed in cultured prostate cancer cells, and circulating prostate tumour cells were isolated from blood samples of patients with AIPC.Results
AIPC cells were derived through prolonged culture in reduced androgen conditions, modelling hormone therapy in patients, and expressed increased levels of Hedgehog signalling proteins. Exposure of cultured AIPC cells to cyclopamine, which inhibits Hedgehog signalling, resulted in inhibition of cancer cell growth. The expression of the Hedgehog receptor PTCH and the highly prostate cancer–specific gene DD3PCA3 was significantly higher in circulating prostate cancer cells isolated from patients with AIPC compared with samples prepared from normal individuals. There was an association between PTCH and DD3PCA3 expression and the length of androgen-ablation therapy.Conclusions
Our data are consistent with reports implicating overactivity of Hedgehog signalling in prostate cancer and suggest that Hedgehog signalling contributes to the androgen-independent growth of prostate cancer cells. As systemic anti-Hedgehog medicines are developed, the Hedgehog pathway will become a potential new therapeutic target in advanced prostate cancer. 相似文献18.
Lih-Ming Wong Shabbir M.H. Alibhai Greg Trottier Narhari Timilshina Theodorus Van der Kwast Alexandre Zlotta Nathan Lawrentschuk Girish Kulkarni Robert Hamilton Sarah Ferrara David Margel John Trachtenberg Michael A. Jewett Ants Toi Andrew Evans Neil E. Fleshner Antonio Finelli 《European urology》2014
Background
Many men (21–52%) are reported to have no cancer on the second, also known as the confirmatory, biopsy (B2) for prostate cancer active surveillance (AS). If these men had a reduced risk of pathologic progression, particularly grade related, the intensity of their follow-up could be decreased.Objective
To investigate if men with no cancer on B2 are less likely to undergo subsequent pathologic progression.Design, setting, and participants
Men were identified from our tertiary care center AS prostate cancer database (1995–2012). Eligibility criteria were prostate-specific antigen (PSA) ≤10, cT2 or lower, no Gleason grade 4 or 5, three or fewer positive cores, and no core >50% involved. Only patients with three or more biopsies were selected and then dichotomized on cancer status (yes or no) at B2.Intervention
AS.Outcome measurements and statistical analysis
Pathologic progression was defined as grade (advancement in Gleason score) and/or volume (more than three positive cores, >50% core involved). Progression-free survival was compared. Predictors of progression were investigated using a Cox proportional hazards model.Results and limitations
Of the 286 patients remaining on AS after B2, 149 (52%) had no cancer and 137 (48%) had cancer. The median follow-up after B2 was 41 mo (interquartile range [IQR]: 26.5–61.9). Progression-free survival at 5 yr was 85.2% versus 67.3% for negative B2 versus cancer on B2, respectively (p = 0.002). Men with no cancer at B2 had a 53% reduction in risk of subsequent progression (hazard ratio [HR]: 0.47; 95% confidence interval [CI], 0.29–0.77; p = 0.003). Subanalysis showed prognostic indicators of volume-related progression were absence of cancer (HR: 0.36; 95% CI, 0.20–0.62; p = 0.0006) and PSA density (HR: 1.79; 95% CI, 1.12–2.89; p = 0.01). The only predictor of grade-related progression was age (HR: 1.05; 95% CI, 1.00–1.10; p = 0.04). Retrospective analysis was the major limitation of the study.Conclusions
Absence of cancer on B2 is associated with a significantly decreased risk of volume-related but not grade-related progression. This must be considered when counseling men on AS. 相似文献19.
Michael Seitz Amita Shukla-Dave Anders Bjartell Karim Touijer Alessandro Sciarra Patrick J. Bastian Christian Stief Hedvig Hricak Anno Graser 《European urology》2009
Context
Magnetic resonance imaging (MRI) combined with magnetic resonance spectroscopy imaging (MRSI), dynamic contrast-enhanced MRI, and diffusion-weighted MRI emerged as promising tests in the diagnosis of prostate cancer, and they show encouraging results.Objective
This review emphasizes different functional MRI techniques in the diagnosis of prostate cancer and includes information about their clinical value and usefulness.Evidence acquisition
The authors searched the Medline, Embase, and Cochrane Library databases. There were no language restrictions. The last search was performed in October 2008.Evidence synthesis
The combination of conventional MRI with functional MRI techniques is more reliable for differentiating benign and malignant prostate tissues than any other diagnostic procedure. At present, no guideline is available that outlines which technique is best in a specific clinical situation. It also remains uncertain whether improved spatial resolution and signal-to-noise ratio of 3-T MRI will improve diagnostic performance.Conclusions
A limited number of small studies suggest that functional MRI may improve the diagnosis and staging of prostate cancer. This finding needs further confirmation in larger studies, and cost-effectiveness needs to be established. 相似文献20.
Liam Bourke Stephen Gilbert Richard Hooper Liz A. Steed Miland Joshi Jim W.F. Catto John M. Saxton Derek J. Rosario 《European urology》2014