Prostate Biopsy Specimens Research Articles

First results of the double-blind randomized placebo-controlled multicenter clinical trial of DIM-based therapy designed as personalized approach to reverse prostatic intraepithelial neoplasia (PIN).

BackgroundTargeted pharmacological correction is used extensively in medical practice today. 3,3'-Diindolylmethane (DIM) is known as a substance with various anticancer properties. An interim study of the efficacy of a new drug Infemin on the basis of diindolylmethane (DIM) with improved bioavalability has been conducted.MethodsThe clinical trial had a multicenter, randomized, placebo-controlled, double-blind design and was carried out in two parallel groups. The interim analysis of data included 21 patients diagnosed with a high-grade prostatic intraepithelial neoplasia (PIN). Group 1 (11 patients) received Infemin in a dose of 900 mg of DIM a day, and group 2 (10 patients) received placebo. To assess the efficacy of therapy, the analysis of morphological index (MI) changes based on the results of histological examinations of prostate biopsy specimens was performed, and a proportion of patients with persistent PIN in 12 months after Infemin initiation was calculated. Researchers also evaluated prostate size, urodynamic parameters (Qmax, Qave, Vres), IPSS, and QoL (quality of life) indices and International Index of Erectile Function (IIEF) at 3, 6, 9, and 12 months after the Infemin administration start.ResultsAfter 12 months of treatment in the Infemin group, MI decreased from 0.50 to 0.08, while in the placebo group, it increased from 0.27 to 0.58; the difference between the groups was statistically significant (p = 0.0003, Mann-Whitney test). In 45.5 % of patients in the Infemin group, a complete regression of PIN was also observed, while in the placebo group, PIN regression was not observed in any patients (p = 0.053, Yates’ corrected chi-square). Study results in the Infemin group show improvement of maximal urinary flow rate Qmax (53.3 % increase compared to the initial value); however, the statistical significance was not reached (p = 0.180, Mann-Whitney test) due to the small sample size. Evaluation of other urodynamic parameters, prostate volume, quality of life, symptoms reflecting urination disorder, and erectile dysfunction symptoms did not reveal significant differences between the Infemin and placebo groups either which is probably due to the small sample size.ConclusionsThe intermediate results of the 21 patients in this multicenter, randomized, placebo-controlled, double-blind study show that Infemin may be a promising drug candidate in patients with high-grade PIN.Trial registration www.chictr.org.cn ChiCTR-INR-15007496

PD08-12 PROGNOSTIC VALUE OF PERCENT GLEASON GRADE 4 IN PROSTATE BIOPSY SPECIMENS AFTER RADICAL PROSTATECTOMY

You have accessJournal of UrologyProstate Cancer: Localized: Active Surveillance III1 Apr 2016PD08-12 PROGNOSTIC VALUE OF PERCENT GLEASON GRADE 4 IN PROSTATE BIOPSY SPECIMENS AFTER RADICAL PROSTATECTOMY Adam Cole, Rohit Mehra, Daniel Spratt, Ganesh Palapattu, Chang He, Scott Tomlins, Alon Weizer, Angela Wu, Felix Fang, Jeffrey Montgomery, Lakshmi Kunju, David Miller, Brent Hollenbeck, John Wei, and Todd Morgan Adam ColeAdam Cole More articles by this author , Rohit MehraRohit Mehra More articles by this author , Daniel SprattDaniel Spratt More articles by this author , Ganesh PalapattuGanesh Palapattu More articles by this author , Chang HeChang He More articles by this author , Scott TomlinsScott Tomlins More articles by this author , Alon WeizerAlon Weizer More articles by this author , Angela WuAngela Wu More articles by this author , Felix FangFelix Fang More articles by this author , Jeffrey MontgomeryJeffrey Montgomery More articles by this author , Lakshmi KunjuLakshmi Kunju More articles by this author , David MillerDavid Miller More articles by this author , Brent HollenbeckBrent Hollenbeck More articles by this author , John WeiJohn Wei More articles by this author , and Todd MorganTodd Morgan More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.02.2828AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES The impact of primary Gleason grade among Gleason score 7 (3+4 vs 4+3) patients has significant impact on prognosis. However, this dichotomization negates the continuous spectrum of absolute percent Gleason grade 4 (G4%). Herein, we report the prognostic value of the G4%, a variable readily discernible from prostate biopsy reports, on cancer-related outcomes of men undergoing radical prostatectomy (RP). METHODS From 2005 - 2013, 1,691 consecutive patients underwent RP at a single institution for clinically localized prostate cancer. G4% was determined from prostate needle biopsies as total tumor length containing Gleason Pattern 4 divided by the total combined tumor length determined by an expert urologic pathologist. Time to biochemical recurrence (BCR), and the presence of adverse RP pathology, defined as primary Gleason 4 or ≥pT3, were correlated to G4% by multivariable logistic and Cox regression analyses. RESULTS Of the 1,691 patients, 517 (30.6%) had adverse pathological features, and 86 (5.6%) had a BCR. Median follow-up time was 1.7 years. Increasing G4% as a categorical variable was closely associated with both adverse pathology and BCR (Figure 1). On multivariable analyses, G4% was a significant predictor of adverse pathology (adjusted odds radio 1.04, 95% CI [1.03 - 1.05] for each 1% increase in G4%) and time to BCR (adjusted hazard ratio 1.02, 95% CI [1.01 - 1.03] for each 1% increase in G4%). G4% was also a significant predictor of adverse pathology in the Gleason 7 (adjusted OR 1.05, 95% CI [1.03 - 1.06]), 3+4 (adjusted OR 1.06, 95% CI: [1.04 - 1.08]), and 4+3 (adjusted OR 1.05, 95% CI [1.03 - 1.06]) subgroup analyses, and a significant predictor of BCR in the Gleason 7 subgroup (adjusted HR 1.02, 95% CI [1.00 - 1.04]). CONCLUSIONS The incremental percentage of Gleason grade 4 disease in prostate biopsy specimens is a significant risk factor for adverse pathology at time of surgery and BCR. Accounting for G4% can improve risk assessment even amongst Gleason 3+4 or Gleason 4+3 patients. Due to the ease of assessing this prognostic variable, G4% may add value in determining intermediate risk patients most ideal for active surveillance. © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e233 Advertisement Copyright & Permissions© 2016MetricsAuthor Information Adam Cole More articles by this author Rohit Mehra More articles by this author Daniel Spratt More articles by this author Ganesh Palapattu More articles by this author Chang He More articles by this author Scott Tomlins More articles by this author Alon Weizer More articles by this author Angela Wu More articles by this author Felix Fang More articles by this author Jeffrey Montgomery More articles by this author Lakshmi Kunju More articles by this author David Miller More articles by this author Brent Hollenbeck More articles by this author John Wei More articles by this author Todd Morgan More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Methylation in benign prostate and risk of disease progression in men subsequently diagnosed with prostate cancer.

In DNA from prostate tumors, methylation patterns in gene promoter regions can be a biomarker for disease progression. It remains unclear whether methylation patterns in benign prostate tissue--prior to malignant transformation--may provide similar prognostic information. To determine whether early methylation events predict prostate cancer outcomes, we evaluated histologically benign prostate specimens from 353 men who eventually developed prostate cancer and received "definitive" treatment [radical prostatectomy (58%) or radiation therapy (42%)]. Cases were drawn from a large hospital-based cohort of men with benign prostate biopsy specimens collected between 1990 and 2002. Risk of disease progression associated with methylation was estimated using time-to-event analyses. Average follow-up was over 5 years; biochemical recurrence (BCR) occurred in 91 cases (26%). In White men, methylation of the APC gene was associated with increased risk of BCR, even after adjusting for standard clinical risk factors for prostate cancer progression (adjusted hazard ratio (aHR) = 2.26; 95%CI 1.23-4.16). APC methylation was most strongly associated with a significant increased risk of BCR in White men with low prostate specific antigen at cohort entry (HR = 3.66; 95%CI 1.51-8.85). In additional stratified analyses, we found that methylation of the RARB gene significantly increased risk of BCR in African American cases who demonstrated methylation of at least one of the other four genes under study (HR = 3.80; 95%CI 1.07-13.53). These findings may have implications in the early identification of aggressive prostate cancer as well as reducing unnecessary medical procedures and emotional distress for men who present with markers of indolent disease.

MiR-24 regulates CDKN1B/p27 expression in prostate cancer.

MicroRNAs (miRNAs) are small, non-coding RNA molecules with an important role in cancer. In prostate cancer, several miRNAs are expressed abnormally suggesting they may be useful markers for diagnosis, prognosis, and potential therapeutic intervention in this disease. However, the contribution of individual miRNAs to the development and progression of this disease remains poorly understood. This study investigated the role of miR-24, which has not been extensively studied in relation to prostate cancer. We used PCR to investigate the expression of miR-24 in a panel of prostate cancer cell-lines and in a series of clinical prostate biopsy specimens. The biological significance of miR-24 expression in prostate cancer cells was assessed by a series of in vitro bioassays and the effect on proposed targets p27 (CDKN1B) and p16 (CDK2NA) was investigated. We showed that miR-24 expression was significantly lower in prostate cancer cell lines compared to a normal prostate epithelial cell line. Decreased expression of miR-24 was also more frequently observed in both needle core and prostatectomy tumor tissue relative to matched normal tissue. Low miR-24 expression correlated with high PSA serum levels and other markers of increased prostate cancer progression. Importantly, over-expression of miR-24 inhibited cell cycle, proliferation, migration, and clonogenic potential of prostate cancer cells, as well as inducing apoptosis. p27 and p16 were confirmed as targets of miR-24 in prostate cancer cells and a significant inverse correlation between miR-24 and p27 was revealed in clinical prostatectomy specimens. These findings provide evidence that miR-24 has a tumor suppressor role in prostate cancer and also targets p27 and p16 in prostate cancer cells. We propose that it may be a useful progression biomarker or focus of therapeutic intervention for this disease.

Primary Synovial Sarcoma of the Prostate Gland: A Review of the Literature

Background : Primary synovial sarcoma of the prostate gland (PSSP) is rare and most clinicians would be unfamiliar with its biological behaviour. Aim: To review the literature on PSSP. Methods: Various internet data bases were searched. Literature Review: PSSP is extremely rare with less than 10 cases reported; affects both young and older men; its diagnosis may be made incidentally following histological and cytogenetics examinations of prostate biopsy or prostatectomy specimens which show: A specific chromosomal translocation t(X; 18; p11; q11); Uniform spindle and oval cells which have formed interlacing fascicles that mimic fibrosarcoma. The compact fascicles of tumour cells focally alternate with hypocellular myxoid tissue which mimic peripheral nerve sheath tumours. Focal pericytomatous pattern of polygonal cells arranged around dilated, thin-walled blood vessels. PSSP tumour cells on immunohistochemical staining, stain positively with: Vimentin (most of the cells), EMA (focal positivity), Bcl-2 (strong positivity), CD99 (strong positivity), Ecadherin (strong positivity), cytokeratin (focal positivity), CD 56 and TLE/TLE1. There is no consensus opinion on treatment of PSSP which is an aggressive tumour with poor outcome. However, an aggressive radical surgical treatment by

A Review on Primary Angiosarcoma of the Prostate Gland: An Update

Primary angiosarcoma of the prostate (PASOP) is a very rare tumour which most clinicians have not encountered and may be unaware of Literature of PASOP was reviewed by obtaining information from various internet data bases including: Google, Google Scholar, Educus, and PUB Med. Less than 20 cases of PASOP have been reported. PASOP may present in a male child or adult with lower urinary tract symptoms, dysuria, haematuria, pain and constipation. There may be in some cases a history of prior radiotherapy for adenocarcinoma of prostate. Diagnosis is based upon histological examination of prostate biopsy specimens which tend to reveal: proliferative vascular channels that are lined by atypical multi-layered or atypical solid endothelial cells, variable pleomorphic tumour cells ranging from spindle cells to large/plump cells; nuclei which are large and pleomorphic and which contain clumped chromatin and prominent nucleoli; mitotic figures of which some may look atypical are frequently seen. PASOPs on immunohistochemical staining tend to stain positively for CD34, Factor 8 (Factor VIII), Vimentin. PASOPs on immunohistochemical staining tend to exhibit negative staining for PSA, Keratin and S-100. Surgical resection with surgical margins that are clear of tumor has been shown to be the treatment associated with a chance of long-term survival but a number of reported cases of PASOP at the time of initial diagnosis had presented with metastatic disease or locally advanced disease and curative surgery

Core 2 β-1, 6-N-acetylglucosaminyltransferase-1 expression in prostate biopsy specimen is an indicator of prostate cancer aggressiveness

IntroductionTo avoid over-treatment of early stage prostate cancer (PCa), predictive biomarkers for PCa aggressiveness which can be obtained during pre-treatment evaluation are essential. Core 2 β-1, 6-N-acetylglucosaminyl-transferase-1 (GCNT1) is a key enzyme that forms core 2 branched O-glycans, the expression of which is associated with aggressive potential of prostate cancer. We examined whether GCNT1 expression in prostate biopsy specimen can predict cancer recurrence after radical prostatectomy for the patients with with PCa. We then investigated molecular background for aggressive malignant potential mediated by GCNT1 expression. MethodsParaffin-embedded PCa biopsy specimens were immunohisto-chemically tested for GCNT1 expression using an anti-GCNT1 monoclonal antibody. We also examined the role of GCNT1 in PCa progression using cell lines which express high or low levels of GCNT1. ResultsGCNT1 expression correlated with D′ Amico's recurrence risk classification. The GCNT1-positive rate in organ confined PCa was significantly lower than that in PCa with extra-prostatic extension. GCNT1-negative tumors were associated with significantly better prostate-specific antigen (PSA)-free survival compared with GCNT1-positive tumors. Multivariate analysis revealed that GCNT1 expression status was an independent risk factor for PSA recurrence after radical prostatectomy. Subsequent basic study revealed that GCNT1-over-expressing cells produced a significantly larger amount of growth factors when co-cultured with prostate stromal cells compared with GCNT1-knocked down cells and formed larger tumors. ConclusionsGCNT1 expression in prostate biopsy specimen is a significant and independent predictor of recurrence after radical prostatectomy, which can be used in pre-treatment decision making for the patient. Further validation study is necessary to establish clinical implication of GCNT1 in management of PCa.

Role of Argyrophilic nucleolar organiser regions [AgNOR's] in preneoplastic lesions of prostate

Aims and objectives: 1. To demonstrate the patterns in different premalignant lesions of prostate. 2. Correlating AgNOR counts with various grades of PIN. Materials and methods: This study was conducted in 83 cases of different prostatic biopsy specimens from 2013 -2015. All biopsy samples were routinely processed and stained with both haematoxylin and eosin and with AgNOR stain. Results: The mean AgNOR count and score of high grade prostatic intraepithelial neoplasia was significantly high when compared to low grade intraepithelial lesion. High grade prostatic intraepithelial lesions associated with nodular hyperplasia or with carcinoma was the same. Conclusion: AgNOR is a simple, cost effective and easy stain to evaluate the proliferative activity of the cell. It can be used as an additional test which will be of immense value regarding the progression of preneoplastic lesions in prostate. Keywords: AgNOR, low grade PIN, high grade PIN.

Up-Regulation of LAT1 during Antiandrogen Therapy Contributes to Progression in Prostate Cancer Cells

Cancer cells require massive amounts of amino acids for survival. LAT1 (L-type amino acid transporter 1) transports essential amino acids, including leucine, which trigger the downstream mTOR (mammalian target of rapamycin) pathway. We examined the association between androgen receptor and LAT1, and the association between LAT1 expression and the acquisition of castration resistance. Western blot and real-time polymerase chain reaction were performed to study protein and mRNA expression. siRNA was used to knock down target genes. A total of 92 prostate biopsy specimens of patients who underwent androgen deprivation therapy were used for immunohistochemical analyses. Cox hazard proportional models and the Kaplan-Meier method were used for statistical analyses. LAT1 was highly expressed in hormone resistant prostate cancer cell lines. Knockdown of LAT1 in LNCaP and C4-2 cells significantly suppressed cell proliferation, migration and invasion. Androgen receptor siRNA or androgen receptor blocking through bicalutamide (10 μM) or MDV3100 (10 μM) significantly increased LAT1 expression (p <0.01). Treatment with dihydrotestosterone (0.1 to 10 nM) reduced LAT1 expression in a dose dependent manner (p<0.01). Bicalutamide/MDV3100 plus siLAT1 synergistically suppressed prostate cancer cell proliferation compared to single inhibition by androgen receptor or LAT1 (p<0.01). High LAT1 expression correlated with significantly shorter prostate specific antigen recurrence-free survival in patients receiving androgen deprivation therapy (p <0.0001). LAT1 expression was an independentpredictor of castration resistance on multivariate analysis (HR 3.56, p=0.0133). The current data may indicate a novel mechanism to acquire castration resistance through activation of the amino acid transporter LAT1.

Outcomes of Gleason score 3 + 4 = 7 prostate cancer with minimal amounts (

The International Society of Urological Pathology Gleason grading system was modified in 2005. Since the modified system was introduced, many cancers that previously would have been categorized as Gleason score (GS) 6 are now categorized as GS 7 based on biopsy specimens that only contain minimal amounts (<6%) of Gleason pattern (GP) 4 tissue. However, the clinical significance of observing <6% of GP 4 tissue in biopsies of GS 7 prostate cancer has not been studied. This study was based on needle biopsy specimens that were categorized as GS 6 or GS 7 and were obtained from patients who underwent radical prostatectomy (RP) with available follow-up data. We assessed the quantity of GP 4 tissue in biopsy specimens of GS 7 prostate cancer. Further, we evaluated the correlation between the quantity of GP 4 tissue and disease progression after RP. GP 4 comprising 26-49% of the specimen, GS 4+3 and percentage of total core tissue scored as positive were significant and independent predictors of prostate-specific antigen (PSA) failure after RP, as assessed using a multivariate Cox regression model that included the quantity of GP 4 in the prostate biopsy specimen, preoperative PSA, perineural invasion, clinical stage, number of positive cores, and percentage of core tissue scored as positive. Cases with GS 3+3 and cases in which the observed GP 4 area was <6% did not differ significantly in terms of biochemical PSA recurrence (BPR) status. In contrast, cases with 6-25% GP 4 tissue, 26-49% GP 4 tissue, and GS 4+3 showed more frequent BPR than cases with GS 3+3. Our data suggest that the quantity of GP 4 tissue in GS 7 cancer has clinical significance. However, there is a need for larger studies of the clinical significance of biopsy specimens that include <6% GP 4 tissue. We should reconsider whether the amount of GP 4 should be included in standart pathology reports.

Diagnosis of prostate cancer by trans rectal ultrasound guided prostate biopsy; an observational study

Introduction Digital rectal examination (DRE) coupled with the measurement of prostate specific antigen (PSA) is widely used for the early diagnosis and monitoring of prostate cancer. In the case of abnormal DRE and/or suspicious PSA value (over 4ng/ml), trans-rectal ultrasound guided prostate biopsy is adopted. Objective was to correlate the ultrasonic appearance with the biochemical markers and histological findings. Methodology This observational study was conducted at the Department of Radiology of Colombo North Teaching Hospital from August 2012 to January 2014. An interviewer administered questionnaire was used to collect data from all patients undergoing biopsy. Demographic data, biochemical markers, ultrasonic appearance and histological findings were recorded. An 18-gauge biopsy needle loaded in a spring-action automatic biopsy device was used to procure six 1.5cm prostate biopsy specimens from both lobes. Results Data from 194 patients were analyzed. Out of patients 30.9% (60) had cancer on biopsy; 33.5% (65) had benign adenomatous hyperplasia(BPH) and 34.5%(67) had chronic prostatitis. Mean (SD) age positive for malignancy was 72.2 (7.6) years. Men with prostate cancer had mean prostate volume of 39.8 ml and mean PSA level of 102.6/dl. 65% (39) of malignant patients had focal lesions. Men with non malignant histology had mean prostate volume of 44.7 ml and mean PSA level of 23.8ng/dl. Ultrasonically focal lesions were identified in 19.7% (26/132) non-malignant males. Presence of focal lesions on imaging was significantly associated with malignancy (p Conclusion Men with prostate cancer were older, had smaller prostate and had higher PSA levels than men with negative biopsies. There is a significant association between finding focal lesion on ultrasound and being diagnosed as malignancy in histology.

Optimal method for measuring tumor extent in needle biopsy specimens to identify small-volume prostate cancer.

To compare various methods for measuring tumor extent in prostate biopsy specimens to identify small-volume prostate cancer. A total of 100 radical prostatectomy specimens were retrospectively analyzed. Receiver operating characteristic analysis was used to compare the abilities of prostate-specific antigen density, and four measures of tumor extent in prostate biopsy specimens - positive core number, greatest percentage of cancer in a single core, greatest length of cancer in cores and total length of cancer in cores - to identify small volume prostate cancer. Four definitions of insignificant cancer volume were used in this analysis: index and total tumor volume <0.5 mL, index tumor volume <1.3 mL and total tumor volume <2.5 mL. Multivariate analysis was also used to evaluate variables for predicting small-volume prostate cancer. Total length of cancer in cores had the highest areas under the curve of all the measures defining small-volume prostate cancer: index tumor volume <0.5 mL (0.855), total tumor volume <0.5 mL (0.877), index tumor volume <1.3 mL (0.784) and total tumor volume <2.5 mL (0.818). On multivariate analysis total length of cancer in cores was an independent predictive factor for prostate cancers with index tumor volume <0.5 mL (P < 0.001), <1.3 mL (P < 0.001) and total tumor volume <0.5 mL (P < 0.001), respectively. Our data suggest that total length of cancer in cores is the optimal measure of tumor extent in prostate biopsy specimens for identifying small-volume prostate cancer.

Brachytherapy and radical prostatectomy in patients with early prostate cancer.

this study analyzes the survival of prostate cancer patients cared for at a hospital in Minas Gerais, Brazil according to one of the following treatments: iodine-125 seed implantation or radical prostatectomy. From January 2002 to December 2005, 129 patients underwent either brachytherapy (64 patients) or surgery (65 patients). all had prostate-specific antigen, Gleason scores and clinical stage recorded prior to treatment. Biochemical relapse was defined as prostate-specific antigen (PSA)>0.4 ng/mL for radical prostatectomy, and any elevation equal or higher than 2 ng/mL over the PSA nadir for implanted patients. To analyze the effect of treatment on biochemical recurrence-free survival (BRFS), Kaplan-Meier curves and Cox regression were generated. Mean follow-up time was 56.1 months for patients with the implant, and 26.6 months for those operated on. BRFS in 5 years was 69% (95% CI: 58.18-77.45) for the whole cohort. when stratified according to treatment, survival of patients who had undergone brachytherapy (79.70%) was higher to those operated on (44.30%; p value= 0.0056). Upon multivariate analysis, independent predictors were iPSA (HR: 2.91, 95% CI: 1,32-6,42), Gleason score (HR: 2.18, 95% CI: 1,00-4,81) and treatment modality (HR: 2.61, 95% CI: 1.18-5,75). Risk of biochemical failure was higher with surgery than brachytherapy, which may be related to the failure criteria adopted, which is different for each therapy, as well as the high rate of histological progression between preoperative prostate biopsy and surgical specimen. it was found that brachytherapy is a good therapeutic option for low risk prostate cancer.

Comparison of pathological data between prostate biopsy and radical prostatectomy specimen in patients with low to very low risk prostate cancer

ObjectiveTo analyze the correlation between pathological data found in radical prostatectomy and previously performed biopsy in patients at low risk prostate cancer. Material and methodsA descriptive, cross-sectional study was conducted to assess the characteristics of radical prostatectomies performed in our center from January 2012 to November 2014. The inclusion criteria were patients with low-risk disease (cT1c–T2a, PSA≤10ng/ml and Gleason score≤6). We excluded patients who had fewer than 8 cores in the biopsy, an unspecified number of affected cores, rectal examinations not reported in the medical history or biopsies performed in another center. ResultsOf the 184 patients who underwent prostatectomy during this period, 87 met the inclusion criteria, and 26 of these had <3 affected cores and PSA density ≤.15 (very low risk). In the entire sample, the percentage of undergrading (Gleason score ≥7) and extracapsular invasion (pT3) was 18.4% (95% CI 10.3–27.6) and 10.35% (95% CI 4.6–17.2), respectively. The percentage of positive margins was 21.8% (95% CI 12.6–29.9). In the very low-risk group, we found no cases of extracapsular invasion and only 1 case of undergrading (Gleason 7 [3+4]), representing 3.8% of the total (95% CI 0–12.5). Predictors of no correlation (stage≥pT3a or undergrading) were the initial risk group, volume, PSA density and affected cores. ConclusionsProstate volume, PSA density, the number of affected cores and the patient's initial risk group influence the poor pathological prognosis in the radical prostatectomy specimen (extracapsular invasion and Gleason score≥7).

Perineural invasion in prostate biopsy specimens is associated with increased bone metastasis in prostate cancer.

We aimed to evaluate the relationship between perineural invasion (PNI) and bone metastasis in prostate cancer (PCa). We retrospectively reviewed the data of 633 PCas who had whole-body bone scan (WBBS) between 2008 and 2014. We recorded the age, clinical T-stage, total PSA (tPSA) prior to biopsy, Gleason sum (GS), and PNI in transrectal ultrasound guided biopsy (TRUS-Bx) and digital rectal examination findings. Bone metastases were assessed with WBBS and magnetic resonance image if WBBS was suspicious. We divided the patients into two groups according to NCCN criteria: (Group 1) bone scan not indicated, (Group 2) bone scan indicated. There were 262 patients in Group 1 and 371 in 2. There is not significant relationship between PNI and bone metastasis in Group 1. However, there is very limited number of metastatic patients (n = 12) in this group. There is a strong relationship between PNI and bone metastasis in Group 2 (P = 0.001). Sensitivity, specificity and positive predictive value of PNI for bone metastasis were 72.4%, 81.7%, and 77.7%, respectively. In this group, tPSA, GS, positive DRE, and PNI were significant covariates for prediction of bone metastasis in univariate and multivariate analysis (except age). The most powerful predictor was PNI, and it increased the risk of bone metastasis 11-fold. PNI in the TRUS-Bx specimens is the most powerful predictive histopathological feature for bone metastasis, by increasing the risk of bone metastasis 11-fold in NCCN bone scan indicated patients (Group 2).

Association between tumor-associated macrophages and microvessel density on prostate cancer progression.

BackgroundTo evaluate tumor-associated macrophages (TAMs) infiltration and microvessel density as possible prognostic factors related to prostate cancer (PCa) progression.MethodsImmunostaining of TAMs in prostate biopsy specimens was performed using a monoclonal antibody CD68 and microvessel density (MVD) using von Willebrand factor (vWF) from 25 specimens with high-grade prostatic intraepithelial neoplasia (HGPIN) and 25 specimens with PCa after transurethral resection of the prostate (TURP). Six microscopic (×200) fields were selected for TAM counting and six microscopic (×100) fields were selected for MVD counting around the cancer foci. Association between age, preoperative prostate-specific antigen (PSA), pathologic Gleason sum (GS), TAM, MVD, extracapsular extension, and metastasis were assessed using Pearson/Spearman, Student t test/Mann-Whitney U test and one-way analysis of variance/Kruskal-Wallis test.ResultsThe mean of age, PSA, TAMs, and MVD were 69.1 ± 9.9, 67.1 ± 92.4, 26.2 ± 11.9, and 31.4 ± 14.0, respectively, from 50 specimens with PCa and HGPIN. Increasing TAMs number was not correlated with increasing MVD number and there was no significant mean difference statistically (P > 0.05) in TAMs and MVD although the mean of TAMs number was higher in PCa versus HGPIN but significant in PSA level (P < 0.001). In PCa specimens, age, PSA, TAMs, and MVD number were higher in patients with metastatic and extracapsular extension, but not significant statistically (P > 0.005). There was no correlation between TAMs and MVD (P > 0.001).ConclusionsTAMs and MVD had increased PCa but did not provide independent prognostic value. Increasing numbers of TAMs was not always followed by an increase in MVD. HGPIN is the most likely precursor for PCa.

Inflammation in prostate cancer progression and therapeutic targeting.

Chronic inflammation contributes to the onset and progression of human cancer, via modifications in the tumor microenvironment by remodeling the extracellular matrix (ECM) and initiating epithelial mesenchymal transition (EMT). At the biological level, chronically inflamed cells release cytokines that are functionally dictating a constitutively active stroma, promoting tumor growth and metastasis. In prostate cancer, inflammation correlates with increased development of “risk factor” lesions or proliferative inflammatory atrophy (PIA). Chronic inflammation in benign prostate biopsy specimens can be associated with high-grade prostate tumors in adjacent areas. In this article, we discuss the current understanding of the incidence of inflammation in prostate cancer progression and the significance of the process in therapeutic targeting of specific inflammatory signaling pathways and critical effectors during tumor progression. Further understanding of the process of chronic inflammation in prostate tumor progression to metastasis will enable development and optimization of novel therapeutic modalities for the treatment of high-risk patients with advanced disease.

Upper limit of cancer extent on biopsy defining very low-risk prostate cancer.

To investigate how much Gleason pattern 3 cancer prostate biopsy specimens may contain without an increased risk of undetected more aggressive cancer, compared with the risk for cancers fulfilling the National Comprehensive Cancer Network (NCCN) criteria for very low-risk prostate cancer. We identified 1286 men aged <70years in the National Prostate Cancer Register of Sweden who underwent primary radical prostatectomy (RP) for stage T1c or T2 prostate cancer with Gleason pattern ≤3 only, prostate-specific antigen (PSA) level of <10ng/mL and a PSA density of <0.15ng/mL/mL. The association between the extent of cancer in the biopsies (the number and proportion of positive cores and the total cancer length in the cores in millimetres) and the likelihood of Gleason pattern 4-5 in the RP specimen was analysed with logistic regression. In all, 438 (34%) of the 1286 men had Gleason pattern 4-5 in the RP specimen. Increasing number and proportion of positive biopsy cores, as well as increasing biopsy cancer length were both significantly associated with increased risk of upgrading at RP in univariable analysis, but in multivariable analysis only biopsy cancer length remained significant. The 684 men with stage T1c and <8mm cancer had similar risk of upgrading regardless of whether the number of positive biopsy cores was 1-2 or 3-4 (28% vs 27% risk); upgrading was more common among the remaining men (40%, P < 0.01). Men aged <70years with stage T1c prostate cancer and 3-4 biopsy cores with Gleason pattern 3 are not more likely to have undetected Gleason pattern 4-5 cancer than men with 1-2 cores with cancer, provided that the total biopsy cancer length is <8mm. We propose that the definition of very low-risk prostate cancer is widened accordingly.

Inflammation of Prostate and Prostate-Specific Antigen

Noncancerous conditions (e.g., benign prostatic hyperplasia and prostatitis) can elevate serum prostate-specific antigen (PSA) levels, limiting the specificity of PSA screening for prostate cancer. In recent years, several studies have also demonstrated a relationship between chronic prostatitis/chronic pelvic pain syndrome and increased PSA levels. However, in asymptomatic patients, routine screening for this diagnosis is not performed before transrectal biopsy to rule out prostate cancer. These asymptomatic men with elevated PSA levels frequently show evidence of inflammation when their expressed prostatic secretions are examined, or on their prostate biopsy specimens. This raises the problem of appropriate evaluation in the presence of chronic prostatitis and elevated PSA levels not only in prostate cancer screening programs, but also in cancer-negative biopsy findings. Thus, there has been investigation into ways to decrease the confounding from inflammation, including repeat PSA measurements after a period of observation or a course of empiric antibiotics. This article reviews the evidence regarding elevations in PSA due to prostatitis and describes the controversy over the optimal approach to reduce its confounding impact on prostate cancer screening. Nowadays, it appears that in patients with prostatic inflammation and increased PSA, an antimicrobial regimen may provide more acceptable initial treatment than proceeding directly to prostate biopsy. Additional evidence is necessary in the form of a randomized clinical trial in which all patients undergo biopsy, regardless of the PSA response to antibiotic or placebo.

Significance of microvessel density in prostate cancer core biopsy

In prostate tumors, angiogenesis, measured as microvessel density, is associated with tumor stage and Gleason score. The aim of this study was determine neovascularization of prostatic adenocarcinomas in core biopsies and corresponding prostatectomies. The study population included 61 patients who underwent radical prostatectomy (RP) for localized prostate carcinoma patients and did not receive chemohormonal, or radiation therapy before surgery. Tumor blocks were immunostained using the endothelial-specific antibody CD31 and subsequently evaluated at x 400 magnification in both biopsies and corresponding prostatectomies. When comparing microvessel density in core biopsies and corresponding prostatectomies, no statistically significant difference was found (p > 0.1). A statistically significant positive correlation was found when determining correlation between microvessel density (as linear and categorical variable, i.e., with the cut-off value of 48) that was associated with the Gleason score (p < 0.05) and tumor stage (p < 0.0001). There was no correlation between microvessel density and preoperative values of serum prostate-specific antigen (PSA) (p > 0.1). Microvessel density can be reliably applied to needle prostate biopsy specimens. Quantification of the microvascular density in biopsies is an accurate pre-operative predictor of tumor stage, discriminating between organ-confined and organ-extending neoplasms.