Higher PSA Levels Research Articles

Is there any association between National Institute of Health category IV prostatitis and prostate-specific antigen levels in patients with low-risk localized prostate cancer?

ABSTRACTPurposeWe investigated the association between National Institute of Health category IV prostatitis and prostate-specific antigen levels in patients with low-risk localized prostate cancer.Materials and MethodsThe data of 440 patients who had undergone prostate biopsies due to high PSA levels and suspicious digital rectal examination findings were reviewed retrospectively. The patients were divided into two groups based on the presence of accompanying NIH IV prostatitis. The exclusion criteria were as follows: Gleason score>6, PSA level>20ng/mL, >2 positive cores, >50% cancerous tissue per biopsy, urinary tract infection, urological interventions at least 1 week previously (cystoscopy, urethral catheterization, or similar procedure), history of prostate biopsy, and history of androgen or 5-alpha reductase use. All patient's age, total PSA and free PSA levels, ratio of free to total PSA, PSA density and prostate volume were recorded.ResultsIn total, 101 patients were included in the study. Histopathological examination revealed only PCa in 78 (77.2%) patients and PCa+NIH IV prostatitis in 23 (22.7%) patients. The median total PSA level was 7.4 (3.5–20.0) ng/mL in the PCa+NIH IV prostatitis group and 6.5 (0.6–20.0) ng/mL in the PCa group (p=0.67). The PSA level was≤10ng/mL in 60 (76.9%) patients in the PCa group and in 16 (69.6%) patients in the PCa+NIH IV prostatitis group (p=0.32).ConclusionsOur study showed no statistically significant difference in PSA levels between patients with and without NIH IV prostatitis accompanying PCa.

MP90-07 THE PHENOMENON OF EPITHELIAL-MESENCHYMAL TRANSITION IS ASSOCIATED WITH THE PROGRESSION OF PROSTATE CANCER

You have accessJournal of UrologyProstate Cancer: Basic Research & Pathophysiology IV1 Apr 2016MP90-07 THE PHENOMENON OF EPITHELIAL-MESENCHYMAL TRANSITION IS ASSOCIATED WITH THE PROGRESSION OF PROSTATE CANCER Jose Pontes, Rafael Coelho, Mauricio Cordeiro, Giuliano Betoni, Luiz Oliveira, Sabrina Reis, Katia Leite, Miguel Srougi, and William Nahas Jose PontesJose Pontes More articles by this author , Rafael CoelhoRafael Coelho More articles by this author , Mauricio CordeiroMauricio Cordeiro More articles by this author , Giuliano BetoniGiuliano Betoni More articles by this author , Luiz OliveiraLuiz Oliveira More articles by this author , Sabrina ReisSabrina Reis More articles by this author , Katia LeiteKatia Leite More articles by this author , Miguel SrougiMiguel Srougi More articles by this author , and William NahasWilliam Nahas More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.02.2551AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES The Prostate Cancer (PC) has a heterogeneous natural history characterized by the broad spectrum of clinical presentation. The current prognostic factors Gleason score, stage and PSA are insufficient to differentiate indolent from aggressive tumors, so the discovery of new prognostic markers is essential. The cell adhesion molecules are important for the maintenance of the benign phenotype and alterations in their expression may play a role in carcinogenesis. E-cadherin promotes strong adhesion between cells while P-,N- and OB-cad promote poor adhesion. The exchange of E-cad by any of the mesenchymal cadherins is characteristic of the epithelial mesenchymal transition phenomenon(EMT) and has been associated with worst prognosis in some cancers. Our aim was to evaluate the occurrence of EMT in the progression of PC and correlate it with the prognosis of locallized PC. METHODS We analyzed the expression of E, N, P and OB-cadherin by immunohistochemistry (H-score) in three tissue microarrays containing samples of 87 locallized primary tumors treated by surgery, 19 lymph node metastases and 28 bone metastases. The criterion for the occurrence of EMT was the H-score of E-cadherin < 4 and at least one of the mesenchimal cadherins with a score> 3. We correlated the occurence of EMT with the PC progression from primary tumor to lymph node and bone metastasis. We also correlated EMT with the classic prognostic factors PSA, Gleason score, pathological stage and with biochemical recurrence in the 87 primary tymor who underwent radical prostatectomy. Biochemical recurrence was defined by a PSA above 0,2ng/ml during follow up. RESULTS We observed a significant increase in the occurrence of EMT according with the progression from primary tumors (42.5%) to lymph node (90%) and bone metastasis (80%) p <0.001. In both metastatic sites the E-cadherin expression was significantly lower than the expression of any of the mesenchymal cadherins (p=0.001). In primary tumor we found positive correlation between EMT and higher PSA levels (p=0.03); and a marginal association with reduced biochemical recurrence free survival time (p=0.1). There was no correlation between EMT and biochemical recurrence, Gleason score or pathological stage. CONCLUSIONS We demonstrated, for the first time in literature, that the occurence of EMT is a phenotypic characteristic of the progression and dissemination of prostate cancer to the metastatic site. The correlation of EMT with higher PSA levels and lower biochemical free survival time also indicates a possible role in the prognosis of locallized PC. © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e1147 Advertisement Copyright & Permissions© 2016MetricsAuthor Information Jose Pontes More articles by this author Rafael Coelho More articles by this author Mauricio Cordeiro More articles by this author Giuliano Betoni More articles by this author Luiz Oliveira More articles by this author Sabrina Reis More articles by this author Katia Leite More articles by this author Miguel Srougi More articles by this author William Nahas More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

FIRST RECORD OF PROSTATIC SCHISTOSOMIASIS IN PERNAMBUCO, BRAZIL: SIGNS OF CHRONICITY IN AN ENDEMIC DISEASE

A esquistossomose acomete, há séculos, a população rural de Pernambuco. Manifestações hepatoesplênicas e neurológicas desta parasitose têm sido frequentemente descritas. No entanto, a esquistossomose da próstata, causada pelo Schistosoma mansoni, nunca havia sido reportada em Pernambuco, o que demonstra a necessidade de registrar este caso. Apresentação do caso: Um paciente de 51 anos, após realizar uma prostectomia parcial por suspeita de neoplasia, foi diagnosticado com esquistossomose da próstata. Após o procedimento cirúrgico, foram coletadas amostras de fezes para a realização de testes parasitológicos que se revelaram positivos para S. mansoni, confirmando que o paciente ainda estava infectado. Exames laboratoriais e clínicos mostraram alterações na função hepática e confirmaram danos hepatointestinais. O acompanhamento ambulatorial do paciente demonstrou que os níveis de antígeno prostático específico permaneceram elevados e, um ano após a primeira intervenção cirúrgica, um exame anatomopatológico mostrou a permanência de lesões fibromatosas esquistossomóticas. Vale ressaltar que, após três tratamentos com praziquantel (abril e julho/2014, fevereiro/2015), os exames de fezes apresentaram-se negativos para S. mansoni. Conclui-se que este diagnóstico acidental de esquistossomose da próstata levanta dúvidas sobre a capacidade dos serviços de saúde para identificar e tratar as formas ectópicas da esquistossomose. A manutenção dos elevados níveis de PSA, mesmo após tratamento cirúrgico e farmacológico, sugerem que os danos causados por S. mansoni aos tecidos são irreversíveis. Portanto, os serviços de saúde devem estar preparados para investigar e diagnosticar os casos, visando à prevenção de sequelas crônicas e ao tratamento precoce.

Age and total and free prostate-specific antigen levels for predicting prostate volume in patients with benign prostatic hyperplasia

Objectives: To investigate the predictive values of free prostate-specific antigen (fPSA), total PSA (tPSA) and age on the prostate volume.Methods: The data of 2148 patients with lower urinary tract symptoms were analyzed retrospectively. The patients who had transrectal ultrasonography guided 10 core biopsies owing to the findings obtained on digital rectal examination and presence of high PSA levels (PSA = 2.5–10 ng/dl), and proven to have BPH histopathologically were included in the study. Age, tPSA, fPSA and the prostate volumes (PV) of the patients were noted.Results: One thousand patients that fulfilled the inclusion criteria were included in the study. The PV of the patients were significantly correlated with age, tPSA and fPSA (p < 0.001 and r = 0.307, p < 0.001 and r = 0.382, p < 0.001 and r = 0.296, respectively). On linear regression model, fPSA was found as a stronger predictive for PV (AUC = 0.75, p < 0.001) when compared to age (AUC = 0.64, p < 0.001), and tPSA (AUC = 0.69, p = 0.013).Conclusions: Although tPSA is an important prognostic factor for predicting PV, the predictive value of fPSA is higher. PV can easily be predicted by using age, and serum tPSA and fPSA levels.

Low serum dehydroepiandrosterone examined by liquid chromatography-tandem mass spectrometry correlates with poor prognosis in hormone-naïve prostate cancer.

There is no consensus on blood adrenal androgen concentrations in men with different stages and pathological grades of prostate cancer. In this study, dehydroepiandrosterone (DHEA) concentrations in blood were examined by ultrasensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS). We analyzed the correlation between DHEA concentrations in blood and clinicopathological findings of prostate cancer. We analyzed 196 men (mean age 70 years) with prostate cancer. The patients underwent systematic needle biopsy, and peripheral blood sampling was conducted for measurement of DHEA. DHEA concentrations in blood were determined using LC-MS/MS method. Patient age, serum prostate-specific antigen, prostate volume measured by ultrasound, and DHEA levels in blood were compared with Gleason score and clinical stage by multivariate analyses. Median value of PSA and prostate volume were 11.5 ng/ml and 27.7 ml, respectively. Median concentration of DHEA in blood was 1,506.4 pg/ml. There was no correlation between serum DHEA and clinical variables such as age, serum PSA, and prostate volume. In multivariate analysis, low serum DHEA levels in prostate cancer patients were significantly related to high Gleason score and advanced clinical stage. Serum PSA levels in prostate cancer patients were also significantly associated with high Gleason score and advanced clinical stage. High serum PSA and low serum DHEA levels were significantly associated with poor prognosis factors in men with hormone-naïve prostate cancer. DHEA concentrations in blood were examined by newly developed ultrasensitive LC-MS/MS. We confirmed that low serum DHEA levels in prostate cancer patients were related to high Gleason score and advanced clinical stage. These results suggest that serum DHEA level may be a useful prognostic factor in prostate cancer patients.

Cell lines from circulating tumor cells.

Circulating tumor cells (CTCs) in the blood of cancer patients have received increasing attention as new diagnostic tool enabling “liquid biopsies” [1]. The perspective to avoid invasive tissue biopsies in the future and obtain similar or even more information by a “simple” blood test has enormous implications in cancer diagnostics [2]. In contrast to the wealth of descriptive studies demonstrating the clinical relevance of CTCs as biomarker, the extremely low concentration of CTCs in the peripheral blood of most cancer patients challenges further functional studies. A prerequisite for functional analyses was therefore the recent advances in our ability to culture CTCs in vitro or expand the CTC pool in vivo using xenografts. The recent manuscript by Cayrefourcq et al. focused on how to establish a colon CTC line and its key characteristics have been reported [3]. In this study, they applied a negative selection for CTC enrichment on blood samples from 71 patients with metastatic colon cancer and cultured all of the CD45(−) remaining cells in non-adherent culture conditions. The authors have provided the experimental proof that CTCs isolated from the blood of a colon cancer patient are able to give rise to a permanent cell line [3]. To our best knowledge, no other group has published the establishment of a permanent cell CTC line or even transient CTC cultures from patients with colon cancer. One reason is that the frequency of CTCs is lower in peripheral blood of colon cancer patients as compared to breast or prostate cancer patients, making it even more difficult to find and grow CTCs in colon cancer. Besides its capacity to expand ex vivo for more than 2 years, the CTC-MCC-41 line showed (i) epithelial properties with stem-cell like characteristics, (ii) an intermediate epithelial/mesenchymal phenotype, (iii) a potential to induce quickly in vitro angiogenesis, (iv) an osteomimetic signature and (v) tumorigenic properties in SCID mice. Importantly, this CTC line shares the main features of the original primary tumor and lymph nodes metastasis of the colon cancer patient. Recent advances in cell culture technologies have opened a new avenue to develop primary cell cultures or permanent cell lines from CTCs. The first publications on CTC cultures dealt with blood from metastatic breast cancer patients. First, Dario Marchetti's group has established primary cultures from CTCs of breast cancer patients with brain metastases [4]. In EpCAM(−) CTCs, a potential signature of brain metastasis comprising “brain metastasis selected markers (BMSMs)” HER2(+)/EGFR(+)/HPSE(+)/Notch1(+) was identified [4]. CTC lines expressing the BMSM signature were highly invasive and able to generate brain and lung metastases in nude mice. Second, Daniel Haber's group has reported on oligoclonal cultures (sustained in vitro for > 6 months) of CTCs isolated from six patients with metastatic breast cancer [5]. Third, in prostate cancer, Gao et al. used a 3D organoid system and succeeded to develop a long-term culture from the peripheral blood of one patient with castration-resistant metastatic disease and high CTC counts and PSA levels [6]. Fourth, Sunitha Nagrath's group focused on lung cancer and developed a novel in situ capture and culture methodology for ex vivo expansion of CTCs using a 3D co-culture model [7]. Figure 1 Establishment of a colon CTC line CTC lines might be used to test new therapeutic approaches. In this context, novel immunotherapeutic strategies have been developed and antibodies against proteins that block the immune response of T-cells such as PD-L1 or CTLA4 have been approved for treatment of cancer patients. Recently, we could show, for the first time, that PD-L1 is frequently expressed on a variable subset of CTCs obtained from metastatic breast cancer patients [8]. Further functional analysis of this interesting subset might reveal CTC-specific immunosuppressive properties. Taken together, the establishment of functional CTC cell line models is now feasible. These models might be useful to test new cancer drugs specifically targeting CTCs. However, to achieve this important goal it is crucial to increase the efficiency of establishing CTC cell lines and xenografts and extend the current studies to patients at earlier stages. The low concentration of CTCs in earlier stage patients might be a bottleneck to identify “metastasis-initiator cells” that may be resistant as well to the immune system by expressing PD-L1. Thus, increasing the yield of current CTC assays along with the development of more efficient culture strategies seems to be of utmost importance.

The prognostic value of SUMO1/Sentrin specific peptidase 1 (SENP1) in prostate cancer is limited to ERG-fusion positive tumors lacking PTEN deletion.

BackgroundPosttranscriptional protein modification by SUMOylation plays an important role in tumor development and progression. In the current study we analyzed prevalence and prognostic impact of the de-SUMOylation enzyme SENP1 in prostate cancer.MethodsSENP1 expression was analyzed by immunohistochemistry on a tissue microarray containing more than 12,400 prostate cancer specimens. Results were compared to tumor phenotype, ERG status, genomic deletions of 3p, 5q, 6q and PTEN, and biochemical recurrence.ResultsSENP1 immunostaining was detectable in 34.5 % of 9,516 interpretable cancers and considered strong in 7.3 %, moderate in 14.9 % and weak in 12.3 % of cases. Strong SENP1 expression was linked to advanced pT stage (p < 0.0001), high Gleason grade (p < 0.0001), positive lymph node status (p = 0.0019), high pre-operative PSA levels (p = 0.0037), and PSA recurrence (p < 0.0001). SENP1 expression was strongly associated with positive ERG fusion status as determined by both in situ hybridization (FISH) and immunohistochemistry as well as with PTEN deletions. Detectable SENP1 immunostaining was found in 41 % of ERG positive and in 47 % of PTEN deleted cancers but in only 30 % of ERG negative and 30 % of PTEN non-deleted cancers (p < 0.0001 each). Deletions of 3p, 5q, and 6q were unrelated to SENP1 expression. Subset analyses revealed that the prognostic impact of SENP1 expression was solely driven by the subgroup of ERG positive, PTEN undeleted cancers. In this subgroup, the prognostic role of SENP1 expression was independent of the preoperative PSA level, tumor stage, Gleason grade, and the status of the resection margin.ConclusionsSENP1 expression has strong prognostic impact in a molecularly defined subset of cancers. This is per se not surprising as the biologic impact of each individual molecular event is likely to be dependent on its cellular environment. However, such findings challenge the concept of finding clinically relevant molecular signatures that are equally applicable to all prostate cancers.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-015-1555-8) contains supplementary material, which is available to authorized users.

P0061 Identification of CD44, α2β1-integrin, and CD133 expressing prostate cancer stem cells in patients from South Korea with prostate cancer

Background Existing therapies for prostate cancer eradicate most cells within a tumour. However, most patients develop androgen-independent disease that cannot be cured. Prostate cancer cells originate from rare stem cells responsible for maintenance of the tumour. Identification of a prostate cancer stem cell provides a useful target from which to develop therapies targeted at these stem cells. Methods Four patients with prostate cancer were included. Their mean age was 72.3 (SD ± 6.6) years. PSA (ng/ml), Gleason score, node involvement, or metastasis in patients were recorded (88.1/7 [4+3], none or bone; 77.7/9 [5+4], iliac node, or bone; 31.4/9 [4+5], none or bone; 299/9 [5+4], iliac node or bone, respectively). Hormonal therapy of prostate cancer was given as a luteinising hormone-releasing hormone agonist and anti-androgen agent. A transurethral resection of the prostate was done and prostate tissue was obtained. Paraffin embedded serial sections (4 μm) were processed for prostate cancer tissue using immunofluorescent staining. Anti-CD133 antibody (1:10, clone 293C3), anti- α 2 β 1-integrin antibody (clone AK-7; TCS), and anti-CD44 (clone G44-26) were used to identify the prostate cancer cells. Stained sections of tissue were then examined under a Olympus laser confocal fluorescence microscope. Findings CD44, α 2 β 1-integrin, and CD133 expressing cancer stem cells were randomly located throughout acini of prostate cancer. High levels of PSA, Gleason score, or lymph node involvement of prostate cancer was not predicted by the presence of cancer stem cells. Interpretation We identified CD133, CD44, and α 2 β 1-integrin expressing cancer stem cells in patients in South Korea with prostate cancer.

Expression of DNA ligase IV is linked to poor prognosis and characterizes a subset of prostate cancers harboring TMPRSS2:ERG fusion and PTEN deletion.

DNA ligases are essential for the maintenance of genome integrity as they are indispensable for DNA replication, recombination and repair. The present study was undertaken to gain insights into the prevalence and clinical significance of ligaseIV (LIG4) expression in prostate cancer. A total of 11,152prostate cancer specimens were analyzed by immunohistochemistry for LIG4 expression. Results were compared to follow-up data, ERG status and deletions at PTEN, 3p13, 5q21 and 6q15. LIG4 expression was predominantly localized in the nucleus of the cells with increased intensities in malignant as compared to benign prostate epithelium. In prostate cancer, LIG4 expression was found in 91% of interpretable tumors, including 12% cancers with weak, 23% with moderate and 56% with strong LIG4 positivity. Strong LIG4 expression was tightly linked to advanced Gleason score (P<0.0001) and positive nodal involvement (P=0.03). There was a remarkable accumulation of strong LIG4 expression in tumors harboring TMPRSS2:ERG fusion and PTEN deletions (P<0.0001 each). High LIG4 expression was also tightly related to early biochemical recurrence when all tumors (P<0.0001) or the subsets of ERG-negative (P=0.0004) or ERG-positive prostate cancers (P=0.006) were analyzed. Multivariate analysis including parameters that are available before surgery demonstrated independent association with biochemical recurrence for advanced Gleason grade on biopsy, high preoperative PSA level, high clinical stage (P<0.0001 each) and for LIG4 immunostaining (P=0.03). Our study identifies LIG4 as a predictor of an increased risk for early PSA recurrence in prostate cancer. Moreover, the strong association with TMPRSS2:ERG fusion and PTEN deletions suggest important interactions between these pathways in prostate cancers.

MP53-08 THE DIAGNOSTIC VALUE OF 68GA-LABELLED PSMA-LIGAND PET/CT IN MEN WITH RECURRENT PROSTATE CANCER

You have accessJournal of UrologyProstate Cancer: Staging I1 Apr 2015MP53-08 THE DIAGNOSTIC VALUE OF 68GA-LABELLED PSMA-LIGAND PET/CT IN MEN WITH RECURRENT PROSTATE CANCER Boris Hadaschik, Ali Afshar-Oromieh, Jan Radtke, Silvan Boxler, Matthias Eder, Klaus Kopka, Jürgen Debus, Markus Hohenfellner, and Uwe Haberkorn Boris HadaschikBoris Hadaschik More articles by this author , Ali Afshar-OromiehAli Afshar-Oromieh More articles by this author , Jan RadtkeJan Radtke More articles by this author , Silvan BoxlerSilvan Boxler More articles by this author , Matthias EderMatthias Eder More articles by this author , Klaus KopkaKlaus Kopka More articles by this author , Jürgen DebusJürgen Debus More articles by this author , Markus HohenfellnerMarkus Hohenfellner More articles by this author , and Uwe HaberkornUwe Haberkorn More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.02.1702AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES One of the key challenges in the management of men with recurrent prostate cancer (PCa) is early detection. Although choline-based PET/CT is widely used for this purpose, there have been numerous studies reporting a low sensitivity and specificity, especially at low PSA levels. Thus, the development of new and improved imaging methods is required. In this context, the prostate-specific membrane antigen (PSMA) has recently received increased attention. A 68Ga-labelled PSMA-targeted radioligand developed by our group (68Ga-PSMA-HBED-CC) has shown promising results and significantly improved contrast when compared to choline PET/CT. However, published data exist for small patient numbers only. The aim of this evaluation was to analyze the diagnostic value of 68Ga-PSMA-PET/CT in a large cohort. METHODS We performed a retrospective analysis of 319 men who received a 68Ga-PSMA-PET/CT from 2011 to 2014. The effects of several possibly interacting variables such as PSA level and doubling-time (PSA-DT), Gleason score (GS), and androgen deprivation therapy (ADT) were evaluated. Tracer uptake was measured in 901 representative tumor lesions. 42 patients underwent histological verification after 68Ga-PSMA-PET/CT. RESULTS In 82.8% of patients at least one lesion indicative for PCa was detected. Tumor-detection was positively associated with PSA level and ADT, but neither GS nor PSA-DT. Mean SUVmax of tumor lesions was 13.3 ± 14.6 (0.7 – 122.5). Amongst men investigated by histology, 416 lesions were true-positive (n=98) or true-negative (n=318). One local relapse and 29 lymph nodes were false-negative. With regard to the lymph nodes, PET-positive lesions lead to systematic node dissection where additional small lymph node metastases were found. These PET-negative lesions were located in the same region as the PET-positive nodes. A lesion-based analysis of sensitivity, specificity, NPV and PPV revealed values of 76.6%, 100%, 91.4% and 100%. Among 116 patients who were available for follow-up, 50 (40%) were treated locally after 68Ga-PSMA-PET/CT and thereby delayed systemic therapy: 27 were treated with external radiation; 19 underwent surgery and four were treated by HIFU. CONCLUSIONS 68Ga-PSMA-PET/CT can detect recurrent PCa in a high number of patients. Our radiotracer is highly specific for PCa and false positive lesions could not be detected. Detection of PCa is improved at higher PSA levels. Interestingly, also ADT had a significantly positive influence on tumor detection rates. Potentially, 68Ga-PSMA-PET/CT can help delay palliative systemic therapy. © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 193Issue 4SApril 2015Page: e638 Peer Review Report Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.MetricsAuthor Information Boris Hadaschik More articles by this author Ali Afshar-Oromieh More articles by this author Jan Radtke More articles by this author Silvan Boxler More articles by this author Matthias Eder More articles by this author Klaus Kopka More articles by this author Jürgen Debus More articles by this author Markus Hohenfellner More articles by this author Uwe Haberkorn More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

DLEC1, a 3p tumor suppressor, represses NF-κB signaling and is methylated in prostate cancer.

Deleted in lung and esophageal cancer 1 (DLEC1), located at 3p22-p21.3, is involved in the carcinogenesis of multiple cancers, but its role in prostate cancer (PrCa) remains unclear. Here, we studied the epigenetic alteration of DLEC1 and its functions in prostate cancer. We found that DLEC1 was highly expressed in normal prostate tissues, normal prostatic epithelium cell line (RWPE-1), and benign prostatic hyperplasia cell line (BPH-1), but frequently downregulated by promoter methylation in PrCa cell lines. Pharmacologic demethylation could restore DLEC1 expression. DLEC1 was downregulated in prostate tumor tissues compared with their adjacent non-malignant tissues. DLEC1 was methylated in 76/110 primary tumors, but rarely in benign prostatic hyperplasia tissues. DLEC1 methylation was associated with higher PSA levels (p = 0.016), higher Gleason scores (p = 0.015), and more advanced tumor stages (p = 0.003). Furthermore, DLEC1 methylation was detected in 11/30 urine sediment samples from PrCa patients, but seldom in ones from BPH patients. Ectopic expression of DLEC1 inhibited the colony formation of PrCa cells, through inducing cell apoptosis. DLEC1 also suppressed PrCa cell migration. Moreover, DLEC1 inhibited NF-κB transcription activity in PrCa and HEK293 cells. Taken together, our data demonstrate that DLEC1 functions as a tumor suppressor but is frequently methylated in prostate cancer. DLEC1 methylation is associated with prostate cancer progression, which could be a non-invasive epigenetic biomarker for PrCa diagnosis. • Promoter methylation of DLEC1 is a potential prognostic biomarker for PrCa. • DLEC1, a functional tumor suppressor, is frequently methylated in PrCa. • DLEC1 suppresses prostate cancer growth and metastatic behavior. • DLEC1 mediates tumor-suppressive activities through NF-κB signaling.

Radical prostatectomy vs radiotherapy in high-risk prostate cancer patients: two centre experience

Background/objectiveThere are no randomized trials on the comparative effectiveness of radical prostatectomy (RP) and radiotherapy (RT) for high-risk prostate cancer. Our aim was to compare treatment outcomes of high-risk prostate cancer after RP and RT, including overall survival (OS), biochemical-progression-free survival (bPFS) and disease-progression-free survival (dPFS), using two cancer treatments centers’ patient data.MethodsData on high-risk prostate cancer patients between 2005 and 2009 were retrospectively reviewed in two cancer centers: National Cancer Institute, Vilnius, Lithuania and N.N. Alexandrov National Cancer Centre of Belarus, Minsk, Belarus; 210 patients were included in the study group treated with RP (n = 174) or RT (n = 36). The mean follow-up time was 5.6 and 6.6 years, respectively.ResultsLower T stage was an independent predictor of better OS (p = 0.01) and bPFS (p = 0.03). Only the highest Gleason score ≥8 was significantly predictive of a worse OS (p = 0.05), bPFS (p = 0.02) and dPFS (p = 0.001). A high PSA level was predictive of a worse bPFS (p = 0.007 for PSA ≥20) and dPFS (p = 0.008 for ≥20). The treatment modality in this study was insignificant after T stage, Gleason score and PSA level adjustment for OS, bPFS survival and dPFS survival (p = 0.17, p = 0.39, p = 0.20).ConclusionsThe T stage, Gleason score and pretreatment PSA level are significant factors for OS, bPFS survival, and dPFS survival of highrisk prostate cancer patients. Treatment option (RP or RT) was not an independent predictor of survival in this study.

PSMA Ligands for Radionuclide Imaging and Therapy of Prostate Cancer: Clinical Status.

Prostate cancer (PCa) is the most common malignancy in men worldwide, leading to substantial morbidity and mortality. At present, imaging of PCa has become increasingly important for staging, restaging, and treatment selection. Until recently, choline-based positron emission tomography/computed tomography (PET/CT) represented the state-of-the-art radionuclide imaging technique for these purposes. However, its application is limited to patients with high PSA levels and Gleason scores. Prostate-specific membrane antigen (PSMA) is a promising new target for specific imaging of PCa, because it is upregulated in the majority of PCa. Moreover, PSMA can serve as a target for therapeutic applications. Currently, several small-molecule PSMA ligands with excellent in vivo tumor targeting characteristics are being investigated for their potential in theranostic applications in PCa. Here, a review of the recent developments in PSMA-based diagnostic imaging and therapy in patients with PCa with radiolabeled PSMA ligands is provided.

Prevalence and Preventive Measures of Prostate Cancer: A Randomized Study in Public and Private Health Care Sector

Prostate cancer accounts for abnormal or uncontrolled division of cells of prostate in male. It is a slow growing cancer which is usually localized rarely metastasized. The growth rate is varies from slow-moderate to high. It mostly occurs in old age and depends on many other factors like weight, height, diet, habit, environment, genetics, and sexual disease. In a prostate cancer, disease stage cannot find unless the patient has symptoms or signs that the cancer has spread. A high PSA level (normal range 4.0 ng per milliliter or less), or a high Gleason score. Gleason scores have often been categorized into groups that show similar biologic behavior: low-grade (well-differentiated), intermediate-grade, moderate to poorly-differentiated or high-grade. This study aims to evaluate occurrence, causes, problem associated with disease and treatment of this cancer in view of the fact to evaluate consequences responsible to contribute carcinoma of prostate. For this purpose study has been conducted at public and private health care sector (n = 100 patients of prostate cancer).The Gleason score are used to diagnose prostate cancer, 10% of patients have score 5 (4 + 1), 40% of patients have score 7 (4 + 3) or (3 + 4), 44% of patients have score 9 (5 + 4), 6% of patients have score 11 (5 + 6) which shows that mostly prognostic grade II, III IV, V occur. Mostly traditional prostectomy is used as a treatment and 78% of the patients got benefit from it. This study concluded that the prostate cancer is occurs due to age factor (old age), fatty diet , tobacco or alcohol intake, duration of cancer is more than 1 year, past history may also be cause like hepatitis, T.B. mostly. Finding of cancer at score 5, 7, 9, 11 and associated complications are hypertension, urinary tract infection, kidney stones.

Radical prostatectomy vs radiotherapy in high-risk prostate cancer patients: two centre experience

Background/objectiveThere are no randomized trials on the comparative effectiveness of radical prostatectomy (RP) and radiotherapy (RT) for high-risk prostate cancer. Our aim was to compare treatment outcomes of high-risk prostate cancer after RP and RT, including overall survival (OS), biochemical-progression-free survival (bPFS) and disease-progression-free survival (dPFS), using two cancer treatments centers’ patient data.MethodsData on high-risk prostate cancer patients between 2005 and 2009 were retrospectively reviewed in two cancer centers: National Cancer Institute, Vilnius, Lithuania and N.N. Alexandrov National Cancer Centre of Belarus, Minsk, Belarus; 210 patients were included in the study group treated with RP (n = 174) or RT (n = 36). The mean follow-up time was 5.6 and 6.6 years, respectively.ResultsLower T stage was an independent predictor of better OS (p = 0.01) and bPFS (p = 0.03). Only the highest Gleason score ≥8 was significantly predictive of a worse OS (p = 0.05), bPFS (p = 0.02) and dPFS (p = 0.001). A high PSA level was predictive of a worse bPFS (p = 0.007 for PSA ≥20) and dPFS (p = 0.008 for ≥20). The treatment modality in this study was insignificant after T stage, Gleason score and PSA level adjustment for OS, bPFS survival and dPFS survival (p = 0.17, p = 0.39, p = 0.20).ConclusionsThe T stage, Gleason score and pretreatment PSA level are significant factors for OS, bPFS survival, and dPFS survival of highrisk prostate cancer patients. Treatment option (RP or RT) was not an independent predictor of survival in this study.

Early urinary continence recovery after robot-assisted radical prostatectomy in older Australian men.

To compare the recovery of urinary continence (UC) after robot-assisted radical prostatectomy (RARP) in men aged ≥70 and <70 years at 1-year follow-up and to assess for preoperative predictors of UC recovery, as older, healthy men with localised prostate cancer are often denied curative surgical treatment on the grounds of worse UC recovery. In all, 262 patients with prostate cancer having undergone RARP between May 2008 and September 2012, under the care of two consultant urological surgeons at three Melbourne hospitals, were identified. Patients were categorised based on their age ≥70 and <70 years and compared with regards to two endpoints; percentage fully continent and mean pads/day at 4-6 weeks, and 3, 6, 9 and 12 months after RARP. Of the 262 men, 9% (24) were aged ≥70 years. Older men had higher PSA levels (P = 0.007) and clinical stages (P < 0.001) compared with the younger cohort. There were more non-nerve sparing procedures in the older group (P = 0.009) and a shorter mean operative time (P = 0.004). At 4-6 weeks after RARP, the number of pads used per day was greater in older men (P = 0.03) and there was a trend towards fewer older men being fully continent (P = 0.08) than their younger counterparts; however, by 3 months and all time-points thereafter there was no difference. The 12-month UC rates were 89% and 92% for men aged <70 and ≥70 years, respectively. Neither age, body mass index, D'Amico risk group, nerve sparing nor use of Rocco suture were predictors of time to UC recovery. UC recovery after RARP in men aged ≥70 years appears comparable to younger men and therefore not a reason to deny older men with a reasonable life-expectancy curative surgical treatment of localised prostate cancer.

Loss of somatostatin receptor subtype 2 in prostate cancer is linked to an aggressive cancer phenotype, high tumor cell proliferation and predicts early metastatic and biochemical relapse.

Somatostatin receptor subtype 2 (SSTR2) is the most frequently expressed SSTR subtype in normal human tissues. SSTR2 expression is differentially regulated in various tumor types and therapeutic somatostatin analogs binding to SSTR2 are in clinical use. In prostate cancers highly contradictory results in terms of SSTR2 expression and its consequences have been published over the past years. The aim of this study was to clarify prevalence and clinical significance of SSTR2 expression in prostate cancer. Therefore, quantitative immunohistochemistry (IHC) using a tissue microarray containing samples from 3,261 prostate cancer patients with extensive clinical and molecular cancer characteristics and oncological follow-up data was performed. IHC data was compared to publicly available Gene Expression Omnibus datasets of human prostate cancer gene expression arrays. While membranous SSTR2 staining was always seen in normal prostate epithelium, SSTR2 staining was absent in more than half (56.1%) of 2,195 interpretable prostate cancer samples. About 13% of all analyzed prostate cancers showed moderate to strong cytoplasmic and membranous SSTR2 staining. Staining intensities were inversely correlated with high Gleason grade, advanced pT category, high tumor cell proliferation (p<0.0001 each), high pre-operative PSA levels, (p = 0.0011) and positive surgical margins (p = 0.006). In silico analysis confirmed lower SSTR2 gene expression in prostate cancers vs. normal adjacent tissue (p = 0.0424), prostate cancer metastases vs. primary cancers (p = 0.0011) and recurrent vs. non-recurrent prostate cancers (p = 0.0438). PSA-free survival gradually declined with SSTR2 staining intensity (p<0.0001). SSTR2-negative cancers were more likely to develop metastases over time (p<0.05). In conclusion, most prostate cancers are indeed SSTR2-negative and loss of SSTR2 strongly predicts an unfavorable tumor phenotype and poor prognosis. Therefore, SSTR2 expression seems an important factor in the pathogenesis of prostate cancer and re-introduction of the receptor in SSTR2-negative prostate cancers may feature a promising target for novel gene therapy approaches.

Effects of prostatic inflammation on LUTS and alpha blocker treatment outcomes.

To evaluate the association between prostatic inflammation and lower urinary tract symptoms (LUTS), and to identify the effects of prostatic inflammation on the treatment with an alpha blocker. 111 Participants who were aged ≥ 50 years, the presence of LUTS (maximal flow rate < 20 m/s, IPSS ≥ 11), and an elevated PSA level (3-20 ng/mL) were treated with tamsulosin 0.2mg once daily for 3 months after prostate biopsies. Prostatic inflammation was scored as none (0), mild (I), moderate (II), or marked (III). LUTS parameters including urine flow rates, IPSS, PSA, and prostate volume were evaluated. Inflammation grading resulted in 25, 60, and 26 patients that were grade 0, I, and II, respectively. Lower grade inflammation was related to higher urine flow rate at baseline. Patients with higher inflammation grades had larger prostate volumes, larger total and transitional zone volumes, and higher PSA levels. Overall, urine flow rates and residual urine volume were improved after 3 months of alpha blocker therapy. Eighty percent of patients with grade 0 inflammation, 73% of patients with grade I inflammation, and 92.3% of patients with grade II inflammation showed improvement of LUTS after treatment. Longer duration of treatment was related to a decreased chance of improvement of LUTS. Patients with increased IPSS voiding subscales could be predictive of improvement of LUTS. Patients with high grade inflammation had lower flow rates and higher prostatic volumes than patients with low grade inflammation. Inflammation grade did not affect the outcomes of alpha blocker treatment.

Complications and outcomes of salvage robot‐assisted radical prostatectomy: a single‐institution experience

To determine the peri-operative outcomes of men undergoing salvage robot-assisted prostatectomy (RARP) and to examine the complications, functional consequences and need for additional treatments after salvage RARP. At total of 51 consecutive patients underwent salvage RARP after previous failed local therapy. Biochemical recurrence (BCR) was defined as two postoperative PSA measurements ≥0.2 ng/mL. Complications at any time postoperatively were recorded prospectively using a modified Clavien system. The Kaplan-Meier method was used for survival estimation, and regression models were used to identify the predictors of BCR or progression-free survival (PFS) and complications. The median age at salvage RARP was 68 years and a median of 68 months had elapsed from the time of primary treatment. The median follow-up was 36 months. The median operation duration was 179 min with a median estimated blood loss of 175 mL. In all, 50% of patients had pathological stage 3 disease and positive surgical margins were found in 31% of patients. The estimated 3-year BCR-free or PFS was 57%. The overall complication rate was 47%, with a 35% major complication rate (Grade III-V). Potency was maintained in 23% of preoperatively potent patients and 45% of all patients regained urinary control. No clinical variables were predictive of major complications, but all patients with postoperative bladder neck contracture were incontinent. A higher PSA level and extracapsular extension were significantly associated with BCR or progression (P < 0.01). Salvage RARP provides oncological control with potential avoidance of systemic non-curative therapy. Complication, incontinence and erectile dysfunction rates are significant but frequently correctable. This reinforces the need for proper patient counselling and selection.

Lactate dehydrogenase 5 isoenzyme overexpression defines resistance of prostate cancer to radiotherapy

Background:Radiotherapy provides high-cure rates in prostate cancer. Despite its overall slow clinical growth, high proliferation rates documented in a subset of tumours relate to poor radiotherapy outcome. This study examines the role of anaerobic metabolism in prostate cancer growth and resistance to radiotherapy.Methods:Biopsy samples from 83 patients with prostate cancer undergoing radical hypofractionated and accelerated radiotherapy were analysed for MIB1 proliferation index and for lactate dehydrogenase isoenzyme LDH5, a marker of tumour anaerobic metabolism. Ninety-five surgical samples were in parallel analysed. Correlation with histopathological variables, PSA and radiotherapy outcome was assessed. Dose–response experiments were performed in PC3 and DU145 cancer cell lines.Results:High MIB1 index (noted in 25% of cases) was directly related to Gleason score (P<0.0001), T3-stage (P=0.0008) and PSA levels (P=0.03). High LDH5 (noted in 65% of cases) was directly related to MIB1 index (P<0.0001), Gleason score (P=0.02) and T3-stage (P=0.001). High Gleason score, MIB1, LDH5 and PSA levels were significantly related to poor BRFS (P=0.007, 0.01, 0.03 and 0.01, respectively). High Gleason score (P=0.04), LDH5 (P=0.01) and PSA levels (P=0.003) were significantly related to local recurrence. MIB1 and T-stage did not affect local control. Silencing of LDHA gene in both prostate cancer cell lines resulted in significant radiosensitisation.Conclusions:LDH5 overexpression is significantly linked to highly proliferating prostate carcinomas and with biochemical failure and local relapse following radiotherapy. Hypoxia and LDHA targeting agents may prove useful to overcome radioresistance in a subgroup of prostate carcinomas with anaerobic metabolic predilection.