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1.

Introduction

To reduce unnecessary prostate biopsies while using novel tests judiciously, we created a tool to predict the probability of clinically significant prostate cancer (CSPC) vs. low-risk prostate cancer or negative biopsy (i.e., when intervention is likely not needed) among men undergoing initial or repeat biopsy.

Methods

Separate models were created for men undergoing initial and repeat biopsy, identified from our institutional biopsy database and the placebo arm of the REDUCE trial, respectively, to predict the presence of CSPC (Gleason≥7 or>33% of cores involved). Predictors considered included age, race, body mass index, family history of prostate cancer, digital rectal examination, prostate volume, prostate-specific antigen (PSA), free-to-total PSA, presence of high-grade prostatic intraepithelial neoplasia or atypical small acinar proliferation on prior biopsy, number of prior biopsies, and number of cores previously taken. Multivariable logistic regression models that minimized the Akaike Information Criterion and maximized out-of-sample area under the receiver operating characteristics curve (AUC) were selected.

Results

Of 7,963 biopsies (initial = 2,042; repeat = 5,921), 1,138 had CSPC (initial = 870 [42.6%]; repeat = 268 [4.5%]). Age, race, body mass index, family history, digital rectal examination, and PSA were included in the initial biopsy model (out-of-sample AUC = 0.74). Age, prostate volume, PSA, free-to-total PSA, prior high-grade prostatic intraepithelial neoplasia, and number of prior biopsies were included in the repeat biopsy model (out-of-sample AUC = 0.81).

Conclusion

These prediction models may help guide clinicians in avoiding unnecessary initial and repeat biopsies in men unlikely to harbor CSPC. This tool may also allow for the more judicious use of novel tests only in patients in need of further risk stratification before deciding whether to biopsy.  相似文献   

2.

Objective

The PSA-age volume (PSA-AV) score was calculated by multiplying the age and prostate volume and then dividing the total by the prebiopsy PSA level. The aim of this study was to evaluate the effect on the sensitivities of PSA and PSA-AV score of International Prostate Symptom Score (I-PSS) and nocturia in predicting positive prostate biopsy findings.

Subjects and methods

A total of 1302 biopsies data were divided into two groups according to presence/absence of nocturia. Of these biopsies, 452 biopsies data with I-PSS were also divided into three groups according to severity of I-PSS. The sensitivities, specificities, positive and negative predictive values of the PSA-AV and PSA in all the groups were calculated separately.

Results

Although the sensitivities of PSA and PSA-AV were similar in the patients with nocturia (94.1% and 95.8%, respectively), the sensitivity of PSA-AV (99.2%) was higher than PSA (91.8%) in the patients without nocturia. The sensitivities of PSA in mild, moderate and severe I-PSS group were found to be 100%, 92.9% and 95%, respectively (the sensitivities of PSA-AV were 100%, 94.4% and 88.2%, respectively). While severity of I-PSS was decreasing, although sensitivity of PSA-AV increased regularly, sensitivity of PSA was variable.

Conclusions

All our data shows that if we remove most of the factors which effect PSA such as age, prostate volume, prostatitis and BPH, we may increase the sensitivity of PSA for predicting positive prostate biopsy. Further PSA formulas contain of result of some tests (I-PSS, uroflowmetry or postvoiding residue urine) as well as age and prostate volume should increase the sensitivity and specificity of PSA for detecting prostate cancer.  相似文献   

3.

Background

Current prostate cancer screening guidelines conflict with respect to the age at which to initiate screening.

Objective

To evaluate the effect of prostate-specific antigen (PSA) screening versus zero screening, starting at age 50–54 yr, on prostate cancer mortality.

Design, setting, and participants

This is a population-based cohort study comparing 3479 men aged 50 yr through 54 yr randomized to PSA-screening in the Göteborg population-based prostate cancer screening trial, initiated in 1995, versus 4060 unscreened men aged 51–55 yr providing cryopreserved blood in the population-based Malmö Preventive Project in the pre-PSA era, during 1982–1985.

Outcome measurements and statistical analysis

Cumulative incidence and incidence rate ratios of prostate cancer diagnosis, metastasis, and prostate cancer death.

Results and limitations

At 17 yr, regular PSA-screening in Göteborg of men in their early 50s carried a more than two-fold higher risk of prostate cancer diagnosis compared with the unscreened men in Malmö (incidence rate ratio [IRR] 2.56, 95% confidence interval [CI] 2.18, 3.02), but resulted in a substantial decrease in the risk of metastases (IRR 0.43, 95% CI 0.22, 0.79) and prostate cancer death (IRR 0.29, 95% CI 0.11, 0.67). There were 57 fewer prostate cancer deaths per 10 000 men (95% CI 22, 92) in the screened group. At 17 yr, the number needed to invite to PSA-screening and the number needed to diagnose to prevent one prostate cancer death was 176 and 16, respectively. The study is limited by lack of treatment information and the comparison of the two different birth cohorts.

Conclusions

PSA screening for prostate cancer can decrease prostate cancer mortality among men aged 50–54 yr, with the number needed to invite and number needed to detect to prevent one prostate cancer death comparable to those previously reported from the European Randomized Study of Screening for Prostate Cancer for men aged 55–69 yr, at a similar follow-up. Guideline groups could consider whether guidelines for PSA screening should recommend starting no later than at ages 50–54 yr.

Patient summary

Guideline recommendations about the age to start prostate-specific antigen screening could be discussed.  相似文献   

4.

Objective

We aim to highlight the progression from the early definition of nononcologic outcomes in prostate cancer (PC) to measurement and use of preferences to ensure appropriate treatment decisions in men with localized disease.

Methods

We review the assessment of nononcologic outcomes after PC treatment and ways to use the outcomes to augment patient care.

Results

PC treatments may have similar oncologic efficacy in men with certain clinical features, but they differ in their nononcologic outcomes. Tools to assess these outcomes have been developed and are useful in areas from treatment reimbursement to shared decision-making.

Conclusions

The ability to measure and make useful data on nononcologic outcomes evolved substantially over the past 20 years. Current work suggests that individual preference assessment for nononcologic outcomes is a promising means of matching patients with appropriate treatment.  相似文献   

5.

Objective

To analyze the performance of different radical prostatectomy–based prognostic tools in predicting the biopsy progression in our active surveillance cohort.

Materials and methods

We analyzed 326 patients with biopsy Gleason grade≤6,≤2 positive biopsy cores,≤20% tumor present in any core, prostate-specific antigen<15 ng/dl, and clinical stages T1–T2a all of whom had at least single surveillance biopsy. Probabilities of pathologically relatively aggressive disease were estimated using Partin and Dinh risk tables and Kattan, Truong, and Kulkarni nomograms for each individual patient. Using these predictions, performance of these tools was quantified regarding discrimination, stratification at different cut-points, calibration, and the clinical net benefit.

Results

Predictions of Partin and Dinh tables were not associated with the biopsy progression. The predictive value of Kattan and Truong nomograms was higher when compared with the other tools, although it was significant only on the first and second surveillance biopsies. Both nomograms were able to identify low- and high-risk subgroups within the cohort. Kattan nomogram demonstrated better correlation with the observed rate of progression over the first 3 biopsies and higher clinical net benefit.

Conclusion

Kattan and Truong nomograms demonstrated the best performance in predicting biopsy progression, although their value was largely limited to the first 2 surveillance biopsies. Both tools were able to stratify patients into subgroups with different risks of progression. These nomograms have important differences, which suggest that a more effective predictive model combining the strong sides of both tools and possibly some other variables could be developed.  相似文献   

6.

Objective

The benefits of prostate-specific antigen (PSA)–based prostate cancer screening are controversial. We sought to determine the change in prostate cancer presentation coinciding with the release of the United States Preventative Services Task Force recommendations against screening in a high-volume community-based urology practice.

Methods

Characteristics of men presenting for an elevated PSA at a community urology practice from August 2011 to August 2015 were queried from a prospectively collected database. A retrospective analysis of presenting PSA, Gleason grade at biopsy, and prostatectomy as well as clinical and pathologic stage was performed. Kruskal-Wallis rank sum and chi-square tests were used for analysis.

Results

Referrals for elevated PSA decreased from 933 in year 1 to 816 by year 4 (12.5% decrease) with a concomitant reduction in biopsies performed in newly referred men from 461 to 356 (22.8% decrease, P = 0.02). The proportion of men presenting with PSAs>10 increased from 28.1% to 36.8% (P = 0.009). First-time biopsy-positivity rate increased from 48.4% to 62.4% with a rise in the proportion having Gleason≥7 from 51.6% to 69.7% (P = 0.0001). Of the 578 men who underwent radical prostatectomy, there was a 19.4% increase in Gleason≥7 tumors (P = 0.01).

Conclusions

Our findings demonstrate a decrease in elevated PSA referrals, increase in PSA at the time of referral, decrease in detection of low-risk disease, and increase in detection of intermediate-/high-risk disease in a high-volume, multisite, community-based urology practice, coinciding with the United States Preventative Services Task Force recommendations against PSA screening.  相似文献   

7.
8.

Objective

There is an urgent need to find new biomarkers with higher specificity and sensitivity for using early detection of prostate cancer (PrCa) and reducing recurrent unnecessary biopsy rates, psychological and physical stress on the patient, and costs. Being noninvasive, urine-based tests might be suitable in routine practice. The aim of this study was to report the first whole-genome gene expression analysis in urine samples, as noninvasive method, that were obtained from PrCa, benign prostate hyperplasia (BPH), and control groups by using the microarray system from Turkey, to our knowledge.

Methods

Whole-genome gene expression profiling was conducted in urine samples of 25 patients with PrCa, 24 patients with BPH, and 11 healthy males by using the Illumina Hi Scan microarray system.

Results

The number of probes showing a significant change at the level of expression were 101 and 75 in PrCa-control and BPH-control comparison groups, respectively. Further, 51 of them were the same in both comparison groups. There was no significant change at the level of expression in PrCa-BPH comparison group.

Conclusion

This study revealed several candidate biomarkers for early diagnosis of PrCa and contributed to the literature by detecting the differences of gene expression profiles in urine samples of PrCa-control and BPH-control comparison groups using the microarray. However, further studies are needed in larger groups.  相似文献   

9.

Background

Targeted prostate biopsies are changing the landscape of prostate cancer (PCa) diagnosis with the degree of suspicion on multiparametric magnetic resonance imaging (mpMRI) being a strong predictor of targeted biopsy outcome. Data regarding the rate and potential causes of false-negative magnetic resonance imaging-transrectal ultrasound (MRI-TRUS) fusion–targeted biopsy in patients with highly suspicious mpMRI findings are lacking.

Objectives

To determine the rate of clinically significant PCa detection in repeat targeted biopsy or surgery in patients with highly suspicious mpMRI findings and in an initial negative MRI-TRUS fusion–targeted biopsy.

Materials and methods

In this single-center, retrospective study of prospectively generated data, men with highly suspicious lesions (Likert 5 score) on mpMRI and an initial negative MRI-TRUS fusion–targeted biopsy were reviewed. The rate of PCa detection in a subsequent MRI-TRUS fusion–targeted biopsy or radical prostatectomy was determined. Tumors in the intermediate- and high-risk groups according to the National Comprehensive Cancer Network criteria were considered clinically significant.

Results

A total of 32 men with 38 Likert 5 lesions were identified. Repeat targeted biopsy or surgery detected cancer in 42% (16/38) of the Likert 5 lesions with initial negative targeted biopsy. Most of these cancers were intermediate- (69%; 11/16) or high-risk (25%; 4/16) tumors.

Conclusion

A negative round of targeted biopsies does not exclude clinically significant PCa in men with highly suspicious mpMRI findings. Patients with imaging-pathology disagreement should be carefully reviewed and considered for repeat biopsy or for strict surveillance.  相似文献   

10.

Objectives

Somatic mutations can be present in clonally expanded cell populations in nonmalignant tissues, which are detectable at tissue-level resolution. Some of the mutational changes may arise due to smoking. We aimed to find out changes in carcinogenic gene expressions related to smoking in nonmalignant prostate gland epithelia.

Materials and methods

The patients who came to the Department of Urology at Abant Izzet Baysal University Medical Faculty from December 2006 to December 2009 for prostate biopsy were questioned for cigarette smoking. The patients were divided into 2 groups, namely, smokers and nonsmokers. Paraffin sections were stained immunohistochemically with p53, PTEN, p16INK4a, MSH2, CHK2, RB, and E-cadherin.

Results

Smoking was the main independent factor that had an effect on the immunohistochemical expressions for p53, p16, and PTEN (P = 0.007, P = 0.036, P = 0.015, respectively). Age and inflammation had no statistically significant effects on gene expressions. No difference was found between smokers and nonsmokers for immunohistochemical expressions of E-cadherin, MSH2, RB, and CHK2.

Conclusions

Smoking-related carcinogens can alter the expressions of some suppressor genes in a prostate tissue, and these alterations can be determined immunohistochemically. Alterations in these genes in prostate gland epithelia could possibly increase the risk for prostate carcinoma.  相似文献   

11.

Background

Taxanes are routinely used to treat men with advanced prostate cancer, yet their molecular mode of action is poorly characterized. Taxanes stabilize microtubules and may hence interfere with a plethora of cellular processes, most notably mitosis. However, prostate cancer is typically a slowly growing tumor suggesting that additional processes play a role in the response to taxanes.

Methods

Here, we analyzed the potential effect of taxanes on microtubuli-dependent intracellular transport and signaling processes, specifically, nuclear translocation of the androgen receptor and modulation of the RAS-RAF-MEK-ERK signaling cascade.

Results

We show that the androgen-driven nuclear translocation of the androgen receptor remains virtually undisturbed by docetaxel in prostate cancer cells. However, we found a striking down-regulation of activated ERK1/2 together with enhanced cytotoxicity in both docetaxel or cabazitaxel-treated cells that was comparable to direct MEK kinase inhibition. Remarkably, MEK inhibition alone was less effective in inducing cytotoxicity than taxanes indicating that a down-regulation of activated ERK1/2 may be necessary but is not sufficient for taxane-induced antitumoral effects. In line with this notion, we show in a xenograft mouse model that prostate cancer cells that are resistant to docetaxel overexpress activated ERK1/2. Taken together, our findings underscore that the modulation of ERK1/2 activation, in concert with other mechanisms, plays an important role in taxane-induced antineoplastic effects on prostate cancer cells.

Conclusions

These results suggest at least partially nonoverlapping effects of docetaxel and androgen deprivation therapy and hence help to understand recent clinical findings. A further elucidation of the mode of action of docetaxel would have important implications to optimize current treatment strategies and biomarker development for men with metastatic prostate cancer.  相似文献   

12.
13.

Introduction and objective

The Prostate Imaging Reporting and Data System (PI-RADS) score was developed to evaluate lesions in the peripheral and transition zone on multiparametric magnetic resonance imaging (mpMRI) of the prostate. We aim to determine if the PI-RADS scoring system can be used to evaluate central zone lesions on mpMRI.

Materials and methods

A retrospective review of 73 patients who underwent mpMRI/ultrasound (US) fusion-guided biopsy of 143 suspicious lesions between February 2014 and October 2015 was performed. All patients underwent a 3 T mpMRI. Indications for mpMRI included an abnormal digital rectal examination, PSA velocity >0.75 ng/dl/y, and patients on active surveillance. The mpMRI sequence involved T2-weighted imaging, diffusion-weighted imaging, and dynamic contrast enhancement. Using 3-dimensional model software (Invivo Corporation, Gainesville, FL, USA), a minimum of 3 magnetic resonance imaging (MRI)/US fusion-guided biopsy samples were taken from each prostate lesion seen on mpMRI irrespective of PI-RADS score, using local anesthesia in an outpatient clinic setting.

Results

A total of 73 patients underwent MRI/US fusion-guided biopsy of 85 peripheral zone lesions, 31 transitional zone lesions, and 27 central zone lesions. Only 2 (7%) of central zone lesions were positive for prostate cancer. Both patients had lesions which were graded as PI-RADS 3. Both the patients had multifocal lesions that encompassed≥50% of the central and transition zones on the sagittal view MRI images. Both patients previously had transrectal US-guided biopsy of the prostate which was negative for cancer. Both patients underwent a robotic-assisted laparoscopic prostatectomy, each revealing high-grade cancer.

Conclusions

Lesions involving only the central gland/zone seen on MRI are less concerning for malignancy and should not be given equal weight as peripheral zone lesions. In this series, no lesions involving solely the central gland/zone, regardless of PI-RADS score, was positive for malignancy on MRI/US fusion-guided biopsy. Consideration of a modified PI-RADS scoring system should be given to help identify central zone lesions with malignant potential.  相似文献   

14.

Objectives

Recent literature reports inverse associations with ejaculator frequency and prostate cancer (PC). We sought to explore the relationship between ejaculatory frequency from ages 20 to 50 and subsequent development of aggressive PC.

Material and methods

We conducted a case-control study sampling 2,141 men from private urology practices in Victoria, Australia. Cases were defined as men with high grade or high stage PC and controls being biopsy negative men. Ejaculation frequency recalled at age decades 20, 30, and 40 second was assessed by questionnaire. Unconditional multivariable logistic regression models were used to generate odds ratios (ORs).

Results

An inverse association with ejaculatory frequency at age 30 to 39 was observed (OR per 5-unit increase per week = 0.83, 95% CI: 0.72–0.96) but not at ages 20 to 29 (OR = 1.01, 95% CI: 0.89–1.14) or ages 40 to 49 (OR = 0.95, 95% CI: 0.81–1.12). This result differed between men with new sexual partners after age 30 (OR = 0.77, P = 0.009) and those with no new partners (OR = 0.97, P = 0.8) though the test for a difference between these estimates was not significant (P = 0.11).

Conclusion

We found only weak evidence of an inverse association between ejaculatory frequency in the fourth decade of life and advanced PC, which was not significantly modified by number of new sexual partners. No relationship was found for ejaculatory frequency in the third and fifth decades of life.  相似文献   

15.

Background

The Phoenix definition (PD) and Stuttgart definition (SD) designed to determine biochemical recurrence (BCR) in patients with postradiotherapy and high-intensity focused ultrasound organ-confined prostate cancer are being applied to follow patients after cryosurgery. We sought to identify predictors of BCR using the PD and SD criteria in patients who underwent primary focal cryosurgery (PFC).

Materials and methods

We performed a retrospective review of patients who underwent PFC (hemiablation) at 2 referral centers from 2000 to 2014. Patients were followed up with serial prostate-specific antigen (PSA). PSA levels, pre- and post-PFC biopsy, Gleason scores, number of positive cores, and BCR (PD = [PSA nadir+2 ng/ml]; SD = [PSA nadir+1.2 ng/ml]) were recorded. Patients who experienced BCR were biopsied, monitored carefully or treated at the discretion of the treating urologist. Cox regression and survival analyses were performed to assess time to BCR using PD and SD.

Results

A total of 163 patients were included with a median follow-up of 36.6 (interquartile range: 18.9–56.4) months. In all, 64 (39.5%) and 98 (60.5%) experienced BCR based on PD and SD, respectively. On multivariable Cox regression, the number of positive pre-PFC biopsy cores was an independent predictor of both PD (hazard ratio [HR] = 1.4, P = 0.001) and SD (HR = 1.3, P = 0.006) BCRs. Post-PFC PSA nadir was an independent predictor of BCR using the PD (HR = 2.2, P = 0.024) but not SD (HR = 1.4, P = 0.181). Survival analysis demonstrated a 3-year BCR-free survival rate of 56% and 36% for PD and SD, respectively. Of those biopsied after BCR, 14/26 (53.8%) using the PD and 18/35 (51.4%) using the SD were found to have residual/recurrent cancer. Of those with prostate cancer on post-PFC biopsy, 57.1% of those with BCR by the PD and 66.7% of those with BCR by the SD were found to have a Gleason score ≥7.

Conclusion

Both the PD and the SD may be used to determine BCR in post-PFC patients. However, the ideal definition of BCR after PFC remains to be elucidated.  相似文献   

16.

Background

The neutrophil-lymphocyte ratio (NLR) is a biological marker of inflammation with a significant prognostic value in the field of oncology.

Aim

In this review, we discuss the prognostic value of the NLR in renal cell carcinoma (RCC).

Material and Method

We conducted a literature review of the PubMed database in August 2016. Initial research identified 31 publications. Following full-text screening, 15 studies were finally included: 7 studies concerning metastatic or locally advanced renal cancer, 6 studies dealing with localized renal cancer, 2 articles evaluating the NLR in renal cancer whatever the status of the disease (metastatic or localized).

Results

For localized RCC, an NLR o 3 was predictive of a reduced risk of recurrence (hazard ratio ¼ 1.63 [1.15, 2.29]). The prognostic value of the NLR was stronger for metastatic or locally advanced RCC. An NLR o 3 predicted increased overall survival (hazard ratio ¼ 1.55 [1.36, 1.76]), progression-free survivals (hazard ratio ¼ 3.19 [2.23, 4.57]), and a response to systemic treatment.

Conclusion

In current practice, the NLR is a simple and inexpensive prognostic factor with potential improvement in the prognostic performance of nomograms used in renal oncology.  相似文献   

17.

Objective

Black men are more prone to harbor prostate cancer. They are more likely to succumb to this tumor than their White counterparts and may benefit from early detection and treatment. In this study, we assess the nationwide and regional disparity in prostate-specific antigen (PSA) screening for prostate cancer between Black men and non-Hispanic Whites (NHWs).

Methods

A total of 247,079 (weighted 55,185,102) men, aged 40 to 99 years, who responded to the 2012 and 2014 behavioral risk factor surveillance system surveys were used for our analysis. End points consisted of self-reported PSA screening and self-reported nonrecommended PSA screening within 12 months of the interview. The latter was defined as screening in men with <10-year life expectancy. Available sociodemographic variables were used to predict these end points. The independent predictors from multivariate models were used to calculate the adjusted prevalence of PSA screening and nonrecommended PSA screening on a nationwide and regional level. These numbers were calculated for Blacks and NHWs separately and were compared between the 2 groups.

Results

Prevalence of PSA screening was 30.7% in NHWs vs. 28.1% in Blacks (P<0.001). On a region-based analysis, New England, Middle Atlantic, South Atlantic, East North Central, East South Central, West South Central, and Mountain showed a significantly higher rate of PSA screening in NHWs as compared to Blacks (all P<0.001). Middle Atlantic had a significantly higher prevalence of nonrecommended screening in NHWs as compared to Blacks, whereas South Atlantic, West South Central, and Pacific had a significantly higher prevalence of nonrecommended screening in Blacks as compared to NHWs (all P<0.001). Overall, 43 states performed screening more frequently to NHWs, whereas only 8 states performed it more frequently to Black men. The nonrecommended screening was performed more frequently to NHWs in 19 states, whereas 24 states performed it more frequently to Black men.

Conclusion

Our study demonstrates that on a regional-level (and state-level), there are significant racial differences in overall and nonrecommended PSA screening across the United States. Further research is necessary to identify the reasons for the differences and help overcoming it.  相似文献   

18.

Introduction and objective

Multiparametric magnetic resonance imaging (MRI) and magnetic resonance (MR) -targeted biopsy have a growing role in the screening and evaluation of prostate cancer. We aim to evaluate the current knowledge, attitude, and practice patterns of urologists regarding this new technique.

Methods

An anonymous online questionnaire was designed to collect information on urologists’ beliefs and use of prostate multiparametric MRI and MR-targeted biopsy. The survey was sent to members of the Society of Urologic Oncology, the Endourological Society, and European Association of Urology. Multivariate logistic regression analysis was performed to determine predictors for use of prostate MRI and MR-targeted biopsy.

Results

A total of 302 responses were received (Endourological Society: 175, European Association of Urology: 23, and Society of Urologic Oncology: 104). Most respondents (83.6%) believe MR-targeted biopsy to be moderately to extremely beneficial in the evaluation of prostate cancer. Overall, 85.7% of responders use prostate MRI in their practice, and 63.0% use MR-targeted biopsy. The 2 most common settings for use of MR-targeted biopsy include patients with history of prior negative biopsy result (96.3%) and monitoring patients on active surveillance (72.5%). In those who do not use MR-targeted biopsy, the principal reasons were lack of necessary infrastructure (64.1%) and prohibitive costs (48.1%). On multivariate logistic regression analysis, practice in an academic setting (1.86 [1.02–3.40], P = 0.043) and performing greater than 25 radical prostatectomies per year (2.32 [1.18–4.56], P = 0.015) remained independent predictors for using MR-targeted biopsy.

Conclusions

Most respondents of our survey look favorably on use of prostate MRI and MR-targeted biopsy in clinical practice. Over time, reduction in fixed costs and easier access to equipment may lead to further dissemination of this novel and potentially transformative technology.  相似文献   

19.

Purpose

Increasing evidence has demonstrated that men taking the anticoagulant warfarin have a lower risk of developing prostate cancer. This phenomenon is not observed in other cancers. We sought to determine if the target of warfarin, vitamin K epoxide reductase (VKOR), is expressed in benign and cancerous prostate tissues and if a functional single nucleotide polymorphism (SNP) in the VKOR gene is associated with prostate cancer risk.

Materials and methods

The expression of VKOR was quantified by immunohistochemistry in an institutional series of 54 radical prostatectomy samples and metastatic biopsies, as well as in 40 other cancers and matched benign tissues on a tissue microarray. Genotyping of SNP rs2359612 was performed in a prospective series of 57 patients.

Results

VKOR is highly expressed in benign human prostate epithelial cells but is not expressed or expressed at very low levels in cancerous cells. This expression pattern is unique to prostate cancer. Additionally, the proportion of the carrier C allele of rs2359612 in the patients with prostate cancer was significantly higher than in the population, suggesting an association between this allele and the risk of having a diagnosis of prostate cancer.

Conclusions

The expression of VKOR in benign prostate epithelial cells, along with the association between a functional VKOR SNP and prostate cancer risk, suggests a possible role for VKOR in mediating the effect of warfarin on prostate cancer risk. Larger multi-institutional cohort studies are warranted, as are molecular studies on the role of VKOR in prostate cancer development.  相似文献   

20.

Objectives

To compare serum testosterone and prostate specific antigen (PSA) levels of patients diagnosed of prostate cancer to those with benign prostatic hyperplasia (BPH).

Subjects and methods

One hundred and thirteen male patients with or without LUTS who had indication(s) for prostate biopsies were recruited. Blood samples were analysed for serum testosterone and serum PSA. Prostate sizes were measured and PSA densities calculated before trans-rectal prostate biopsies were performed.

Results

On histology of prostate biopsy specimens, 54 patients (47.8%) had prostate adenocarcinoma while 59 patients (52.2%) had BPH. Serum testosterone levels were lower in the prostate cancer group (23.09 ± 2.31 nmol/L versus 24.37 ± 1.94 nmol/L in the BPH group) but this difference was not statistically significant (p = 0.671). Serum testosterone also did not differ significantly with Gleason grade and Gleason score in patients with prostate cancer.Serum PSA and PSA density (PSAD) values were significantly higher in men with prostate cancer, and also in prostate cancer patients with high grade disease.

Conclusion

Serum testosterone levels of patients with prostate cancer did not significantly differ from those of patients with BPH and were not related to grade in prostate cancer patients.  相似文献   

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