Prostate magnetic resonance imaging-targeted biopsy global grade correlates better than highest grade with prostatectomy grade.

BACKGROUND: Magnetic resonance imaging (MRI)-targeted prostate biopsy has become an increasingly common method of diagnosing prostate cancer. A previous study from our institution demonstrated that the biopsy global Grade Group (gGG, aggregate GG of all positive cores) and highest Grade Group (hGG in any core) both show substantial concordance with the Grade Group at radical prostatectomy (RPGG) while the discordance predominantly consists of upgrading in gGG and downgrading in hGG. We performed a larger cohort study focused on biopsy cases in which gGG and hGG differ, to determine their relative concordance with RPGG. METHODS: We conducted a retrospective review of radical prostatectomy specimens with prior MRI-targeted biopsies from our institution between 2016 and 2020. Separate gGG and hGG were assigned to each MRI-targeted lesion. Targeted lesions with different gGG versus hGG were segregated from those with identical gGG and hGG. The concordance of biopsy GG with RPGG was evaluated using κ coefficient analysis. RESULTS: Of the 489 lesions with MRI-targeted biopsies, 82 (17%) differed in gGG versus hGG. The gGG of 46 (56%), 33 (40%), and 3 (4%) lesions were unchanged, upgraded, and downgraded at radical prostatectomy, respectively (κ= 0.302, weighted κ = 0.334). The hGG of 24 (29%), 9 (11%), and 49 (60%) lesions were unchanged, upgraded, and downgraded at radical prostatectomy, respectively (κ = 0.040, weighted κ = 0.198). When stratified by the biopsy GG, gGG showed the highest concordance in GG2 (61%) and GG3 (54%) lesions. The hGG resulted in substantial downgrading (60%) with less optimal concordance regardless of the biopsy GG. Neither the prebiopsy prostate specific antigen level nor the PI-RADS score was predictive of upgrading of gGG. CONCLUSIONS: When gGG and hGG differ, gGG method more accurately predicts the RPGG than hGG, particularly in GG2 and GG3 lesions which comprised the majority of targeted lesions.

Stimulated Raman histology, a novel method to allow for rapid pathologic examination of unprocessed, fresh prostate biopsies.

INTRODUCTION: Delay between targeted prostate biopsy (PB) and pathologic diagnosis can lead to a concern of inadequate sampling and repeated biopsy. Stimulated Raman histology (SRH) is a novel microscopic technique allowing real-time, label-free, high-resolution microscopic images of unprocessed, unsectioned tissue. This technology holds potential to decrease the time for PB diagnosis from days to minutes. We evaluated the concordance of pathologist interpretation of PB SRH as compared with traditional hematoxylin and eosin (H&E) stained slides. METHODS: Men undergoing prostatectomy were included in an IRB-approved prospective study. Ex vivo 18-gauge PB cores, taken from prostatectomy specimen, were scanned in an SRH microscope (NIO; Invenio Imaging) at 20 microns depth using two Raman shifts: 2845 and 2930 cm-1 , to create SRH images. The cores were then processed as per normal pathologic protocols. Sixteen PB containing a mix of benign and malignant histology were used as an SRH training cohort for four genitourinary pathologists, who were then tested on a set of 32 PBs imaged by SRH and processed by traditional H&E. Sensitivity, specificity, accuracy, and concordance for prostate cancer (PCa) detection on SRH relative to H&E were assessed. RESULTS: The mean pathologist accuracy for the identification of any PCa on PB SRH was 95.7%. In identifying any PCa or ISUP grade group 2-5 PCa, a pathologist was independently able to achieve good and very good concordance (κ: 0.769 and 0.845, respectively; p < 0.001). After individual assessment was completed a pathology consensus conference was held for the interpretation of the PB SRH; after the consensus conference the pathologists' concordance in identifying any PCa was also very good (κ: 0.925, p < 0.001; sensitivity 95.6%; specificity 100%). CONCLUSION: SRH produces high-quality microscopic images that allow for accurate identification of PCa in real-time without need for sectioning or tissue processing. The pathologist performance improved through progressive training, showing that ultimately high accuracy can be obtained. Ongoing SRH evaluation in the diagnostic and treatment setting hold promise to reduce time to tissue diagnosis, while interpretation by convolutional neural network may further improve diagnostic characteristics and broaden use.

Single-cell analysis of localized prostate cancer patients links high Gleason score with an immunosuppressive profile.

BACKGROUND: Evading immune surveillance is a hallmark for the development of multiple cancer types. Whether immune evasion contributes to the pathogenesis of high-grade prostate cancer (HGPCa) remains an area of active inquiry. METHODS: Through single-cell RNA sequencing and multicolor flow cytometry of freshly isolated prostatectomy specimens and matched peripheral blood, we aimed to characterize the tumor immune microenvironment (TME) of localized prostate cancer (PCa), including HGPCa and low-grade prostate cancer (LGPCa). RESULTS: HGPCa are highly infiltrated by exhausted CD8+ T cells, myeloid cells, and regulatory T cells (TRegs). These HGPCa-infiltrating CD8+ T cells expressed high levels of exhaustion markers including TIM3, TOX, TCF7, PD-1, CTLA4, TIGIT, and CXCL13. By contrast, a high ratio of activated CD8+  effector T cells relative to TRegs and myeloid cells infiltrate the TME of LGPCa. HGPCa CD8+  tumor-infiltrating lymphocytes (TILs) expressed more androgen receptor and prostate-specific membran antigen yet less prostate-specific antigen than the LGPCa CD8+  TILs. The PCa TME was infiltrated by macrophages but these did not clearly cluster by M1 and M2 markers. CONCLUSIONS: Our study reveals a suppressive TME with high levels of CD8+ T cell exhaustion in localized PCa, a finding enriched in HGPCa relative to LGPCa. These studies suggest a possible link between the clinical-pathologic risk of PCa and the associated TME. Our results have implications for our understanding of the immunologic mechanisms of PCa pathogenesis and the implementation of immunotherapy for localized PCa.

Chemokine signaling via the CXCR2 receptor reinforces senescence.

Cells enter senescence, a state of stable proliferative arrest, in response to a variety of cellular stresses, including telomere erosion, DNA damage, and oncogenic signaling, which acts as a barrier against malignant transformation in vivo. To identify genes controlling senescence, we conducted an unbiased screen for small hairpin RNAs that extend the life span of primary human fibroblasts. Here, we report that knocking down the chemokine receptor CXCR2 (IL8RB) alleviates both replicative and oncogene-induced senescence (OIS) and diminishes the DNA-damage response. Conversely, ectopic expression of CXCR2 results in premature senescence via a p53-dependent mechanism. Cells undergoing OIS secrete multiple CXCR2-binding chemokines in a program that is regulated by the NF-kappaB and C/EBPbeta transcription factors and coordinately induce CXCR2 expression. CXCR2 upregulation is also observed in preneoplastic lesions in vivo. These results suggest that senescent cells activate a self-amplifying secretory network in which CXCR2-binding chemokines reinforce growth arrest.

Multiparametric magnetic resonance imaging identifies significant apical prostate cancers.

OBJECTIVE: To determine if multiparametric (mp) magnetic resonance imaging (MRI) can identify significant apical disease, thereby informing decisions regarding preservation of the membranous urethra. MATERIALS AND METHODS: Men undergoing radical prostatectomy (RP) between January 2012 and June 2016, who underwent a 12-core transrectal ultrasonography-guided systematic biopsy (SB), preoperative 3-Tesla MRI, and sectioning of the prostate specimen with tumour foci mapping, were extracted from a single surgeon's prospective longitudinal outcomes database. Apical SB and mpMRI lesion results were compared with regard to their ability to predict aggressive tumours in the prostatic apex (PA), defined as prostate cancer grade group >1. RESULTS: Of the 100 men who met the eligibility criteria, 43 (43%) exhibited aggressive prostate cancer in the distal 5 mm of the apex. A Likert score >2 in the apical one-third of the prostate was found to be more reliable than any cancer found on apical SB at detecting aggressive cancer in the apex. On multivariate regression analysis, which included Likert score in the apex, age, prostate-specific antigen (PSA) level, prostate size and presence of any cancer on apical biopsy, only Likert score (P = 0.005) and PSA level (P = 0.025) were significant and independent predictors of aggressive cancer in the distal apex. CONCLUSION: The results of the study showed that MRI was superior to SB at identifying aggressive prostate cancer within the distal PA and may be useful for planning the extent of apical preservation during RP.

Incidence of intraductal carcinoma, multifocality and bilateral significant disease in radical prostatectomy specimens from Japan and United States.

Significant differences, including epidemiologic, clinical, pathologic and genetic, exist between Asian and Caucasian prostate cancer. Detailed pathologic data are, however, scarce. We studied in detail and compared the pathological features of prostate cancer in radical prostatectomy specimens in 228 patients (117 Japan, 111 US). Japanese prostate cancer had a higher Gleason grade group (mean 2.67 vs. 2.42 US, P < 0.05), but lower pathological stage (72 % pT2 and 28 % pT3 vs 55 % pT2 and 45 % pT3 US, P < 0.05). Japanese cancer showed significantly more tumor foci (3.8 vs 2.9 US, P < 0.05), and higher incidence of bilateral significant disease (81.3 % vs. 66.7 % US, P < 0.05). The dominant tumor nodules in Japanese cases had higher Gleason grade group (mean 2.73 vs. 2.40 US, P < 0.05). The incidence of intraductal carcinoma was significantly higher in Japanese patients (35.3 % vs. 12.6 % US, P < 0.01), which was independent of Gleason score (7: 30.9 % Japan vs 11.8 % US, P < 0.01; ≥ 8: 87.5 % Japan vs 28.6 % US, P < 0.01) and tumor stage (pT2: 24.1 % Japan vs 6.6 % US, P < 0.01; pT3: 62.9 % Japan vs 20 % US, P < 0.01). These findings demonstrate distinct pathological features in prostate cancer between Japanese and Caucasian patients, and may have important diagnostic and therapeutic implications.

Fibulin-3 as a blood and effusion biomarker for pleural mesothelioma.

BACKGROUND: New biomarkers are needed to detect pleural mesothelioma at an earlier stage and to individualize treatment strategies. We investigated whether fibulin-3 in plasma and pleural effusions could meet sensitivity and specificity criteria for a robust biomarker. METHODS: We measured fibulin-3 levels in plasma (from 92 patients with mesothelioma, 136 asbestos-exposed persons without cancer, 93 patients with effusions not due to mesothelioma, and 43 healthy controls), effusions (from 74 patients with mesothelioma, 39 with benign effusions, and 54 with malignant effusions not due to mesothelioma), or both. A blinded validation was subsequently performed. Tumor tissue was examined for fibulin-3 by immunohistochemical analysis, and levels of fibulin-3 in plasma and effusions were measured with an enzyme-linked immunosorbent assay. RESULTS: Plasma fibulin-3 levels did not vary according to age, sex, duration of asbestos exposure, or degree of radiographic changes and were significantly higher in patients with pleural mesothelioma (105±7 ng per milliliter in the Detroit cohort and 113±8 ng per milliliter in the New York cohort) than in asbestos-exposed persons without mesothelioma (14±1 ng per milliliter and 24±1 ng per milliliter, respectively; P<0.001). Effusion fibulin-3 levels were significantly higher in patients with pleural mesothelioma (694±37 ng per milliliter in the Detroit cohort and 636±92 ng per milliliter in the New York cohort) than in patients with effusions not due to mesothelioma (212±25 and 151±23 ng per milliliter, respectively; P<0.001). Fibulin-3 preferentially stained tumor cells in 26 of 26 samples. In an overall comparison of patients with and those without mesothelioma, the receiver-operating-characteristic curve for plasma fibulin-3 levels had a sensitivity of 96.7% and a specificity of 95.5% at a cutoff value of 52.8 ng of fibulin-3 per milliliter. In a comparison of patients with early-stage mesothelioma with asbestos-exposed persons, the sensitivity was 100% and the specificity was 94.1% at a cutoff value of 46.0 ng of fibulin-3 per milliliter. Blinded validation revealed an area under the curve of 0.87 for plasma specimens from 96 asbestos-exposed persons as compared with 48 patients with mesothelioma. CONCLUSIONS: Plasma fibulin-3 levels can distinguish healthy persons with exposure to asbestos from patients with mesothelioma. In conjunction with effusion fibulin-3 levels, plasma fibulin-3 levels can further differentiate mesothelioma effusions from other malignant and benign effusions. (Funded by the Early Detection Research Network, National Institutes of Health, and others.).

Stromal androgen receptor in prostate development and cancer.

The androgen receptor (AR) in stromal cells contributes significantly to the development and growth of prostate during fetal stages as well as during prostate carcinogenesis and cancer progression. During prostate development, stromal AR induces and promotes epithelial cell growth, as observed from tissue recombinant and mouse knockout studies. During prostate carcinogenesis and progression, the stromal cells begin to lose AR expression as early as at the stage of high-grade prostatic intraepithelial neoplasia. The extent of loss of stromal AR is directly proportional to the degree of differentiation (Gleason grade) and progression of prostate cancer (PCa). Co-culture studies suggested that stromal AR inhibits the growth of malignant epithelial cells, possibly through expression of certain paracrine factors in the presence of androgens. This functional reversal of stromal AR, from growth promotion during fetal prostate development to mediating certain growth-inhibiting effects in cancer, explains to some extent the reason that loss of AR expression in stromal cells may be crucial for development of resistance to androgen ablation therapy for PCa. From a translational perspective, it generates the need to re-examine the current therapeutic options and opens a fundamental new direction for therapeutic interventions, especially in advanced PCa.

Image Guided Focal Therapy for Magnetic Resonance Imaging Visible Prostate Cancer: Defining a 3-Dimensional Treatment Margin Based on Magnetic Resonance Imaging Histology Co-Registration Analysis.

PURPOSE: We compared prostate tumor boundaries on magnetic resonance imaging and radical prostatectomy histological assessment using detailed software assisted co-registration to define an optimal treatment margin for achieving complete tumor destruction during image guided focal ablation. MATERIALS AND METHODS: Included in study were 33 patients who underwent 3 Tesla magnetic resonance imaging before radical prostatectomy. A radiologist traced lesion borders on magnetic resonance imaging and assigned a suspicion score of 2 to 5. Three-dimensional reconstructions were created from high resolution digitalized slides of radical prostatectomy specimens and co-registered to imaging using advanced software. Tumors were compared between histology and imaging by the Hausdorff distance and stratified by the magnetic resonance imaging suspicion score, Gleason score and lesion diameter. Cylindrical volume estimates of treatment effects were used to define the optimal treatment margin. RESULTS: Three-dimensional software based registration with magnetic resonance imaging was done in 46 histologically confirmed cancers. Imaging underestimated tumor size with a maximal discrepancy between imaging and histological boundaries for a given tumor of an average ± SD of 1.99 ± 3.1 mm, representing 18.5% of the diameter on imaging. Boundary underestimation was larger for lesions with an imaging suspicion score 4 or greater (mean 3.49 ± 2.1 mm, p <0.001) and a Gleason score of 7 or greater (mean 2.48 ± 2.8 mm, p = 0.035). A simulated cylindrical treatment volume based on the imaging boundary missed an average 14.8% of tumor volume compared to that based on the histological boundary. A simulated treatment volume based on a 9 mm treatment margin achieved complete histological tumor destruction in 100% of patients. CONCLUSIONS: Magnetic resonance imaging underestimates histologically determined tumor boundaries, especially for lesions with a high imaging suspicion score and a high Gleason score. A 9 mm treatment margin around a lesion visible on magnetic resonance imaging would consistently ensure treatment of the entire histological tumor volume during focal ablative therapy.

Magnetic Resonance Imaging-Ultrasound Fusion Targeted Prostate Biopsy in a Consecutive Cohort of Men with No Previous Biopsy: Reduction of Over Detection through Improved Risk Stratification.

PURPOSE: MRF-TB (magnetic resonance imaging-ultrasound fusion targeted prostate biopsy) may improve the detection of prostate cancer in men presenting for prostate biopsy. We report clinical outcomes of 12-core systematic biopsy and MRF-TB in men who presented for primary biopsy and further describe pathological characteristics of cancers detected by systematic biopsy and not by MRF-TB. MATERIALS AND METHODS: Clinical outcomes of 452 consecutive men who underwent prebiopsy multiparametric magnetic resonance imaging followed by MRF-TB and systematic biopsy at our institution between June 2012 and June 2015 were captured in an institutional review board approved database. Clinical characteristics, biopsy results and magnetic resonance imaging suspicion scores were queried from the database. RESULTS: Prostate cancer was detected in 207 of 382 men (54.2%) with a mean±SD age of 64±8.5 years and mean±SEM prostate specific antigen 6.8±0.3 ng/ml who met study inclusion criteria. The cancer detection rate of systematic biopsy and MRF-TB was 49.2% and 43.5%, respectively (p=0.006). MRF-TB detected more Gleason score 7 or greater cancers than systematic biopsy (117 of 132 or 88.6% vs 102 of 132 or 77.3%, p=0.037). Of 41 cancers detected by systematic biopsy but not by MRF-TB 34 (82.9%) demonstrated Gleason 6 disease, and 26 (63.4%) and 34 (82.9%) were clinically insignificant by Epstein criteria and a UCSF CAPRA (University of California-San Francisco-Cancer of the Prostate Risk Assessment) score of 2 or less, respectively. CONCLUSIONS: In men presenting for primary prostate biopsy MRF-TB detects more high grade cancers than systematic biopsy. Most cancers detected by systematic biopsy and not by MRF-TB are at clinically low risk. Prebiopsy magnetic resonance imaging followed by MRF-TB decreases the detection of low risk cancers while significantly improving the detection and risk stratification of high grade disease.

False-positive rate of positron emission tomography/computed tomography for presumed solitary metastatic adrenal disease in patients with known malignancy.

PURPOSE: The aim of this study was to determine the diagnostic accuracy of positron emission tomography (PET) in cancer patients undergoing adrenalectomy for presumed metastatic disease, utilizing the gold standard of histopathology. METHODS: We retrospectively reviewed all adrenalectomies for metastatic disease performed at our institution over the last 12 years. Preoperative PET scans were compared with final pathology reports. Statistical analyses were performed with Fisher's exact test for categorical variables and Student's t test for continuous variables. RESULTS: Forty-nine adrenalectomies were performed for metastatic disease. Thirty had preoperative PET imaging and were included in this analysis. Mean age was 65.5 ± 13.6 years (29-91) and 54 % were male. Mean size was 3.8 cm (0.4-7.1). Primary tumor distribution was 61 % (n = 17) pulmonary; 11 % (n = 3) breast; 7 % (n = 2) gastric; 7 % (n = 2) renal; and 4 % (n = 1) each of brain, lymphoma, melanoma, and uterine. Mean standardized uptake value (SUV) was 11 ± 7.3 (3.2-30.0). Final pathology revealed that 80 % (25/30) were positive for metastatic disease and 20 % (5/30) were negative. The positive predictive value of PET in correctly identifying adrenal metastatic disease was 83 % (24 true-positive cases and 5 false-positive cases); there was one false-negative PET. False-positive PET results were not correlated with sex (p = 0.35), age (p = 0.24), or maximum SUV units (p = 0.26). CONCLUSIONS: The 20 % false-positive rate for PET-positive adrenalectomies performed for metastatic disease should warrant its inclusion in preoperative counseling to the patient and interaction with the treating oncologist.

Whole-lesion apparent diffusion coefficient metrics as a marker of percentage Gleason 4 component within Gleason 7 prostate cancer at radical prostatectomy.

PURPOSE: To retrospectively assess the utility of whole-lesion apparent diffusion coefficient (ADC) metrics in characterizing the Gleason 4 component of Gleason 7 prostate cancer (PCa) at radical prostatectomy. MATERIALS AND METHODS: Seventy patients underwent phased-array coil 3T-magnetic resonance imaging (MRI) before prostatectomy. A uropathologist mapped locations and Gleason 4 percentage (G4%) of Gleason 7 tumors. Two radiologists independently reviewed ADC maps, aware of tumor locations but not G4%, and placed a volume-of-interest (VOI) on all slices including each lesion on the ADC map to obtain whole-lesion mean ADC and ADC entropy. Entropy reflects textural variation and increases with greater macroscopic heterogeneity. Performance for characterizing Gleason 7 tumors was assessed with mixed-model analysis of variance (ANOVA) and logistic regression. RESULTS: Among 84 Gleason 7 tumors (G4% 5%-85%, median 30%; 59 Gleason 3+4, 25 Gleason 4+3), ADC entropy was significantly higher in Gleason 4+3 than Gleason 3+4 tumors (R1: 5.27 ± 0.61 vs. 4.62 ± 0.78, P = 0.001; R2: 5.91 ± 0.32 vs. 5.57 ± 0.56, P = 0.004); mean ADC was not significantly different between these groups (R1: 0.90 ± 0.15*10(-3) cm(2) /s vs. 0.98 ± 0.21*10(-3) cm(2) /s, P = 0.075; R2: 1.06 ± 0.19*10(-3) cm(2) /s vs. 1.14 ± 0.16*10(-3) cm(2) /s, P = 0.083). The area under the receiver operating characteristic (ROC) curve (AUC) for differentiating groups was significantly higher with ADC entropy than mean ADC for one observer (R1: 0.74 vs. 0.57, P = 0.027; R2: 0.69 vs. 0.61, P = 0.329). For R1, correlation with G4% was moderate for ADC entropy (r = 0.45) and weak for mean ADC (r = -0.25). For R2, correlation with G4% was moderate for ADC entropy (r = 0.41) and mean ADC (r = -0.32). For both readers, ADC entropy (P = 0.028-0.003), but not mean ADC (P = 0.384-0.854), was a significant independent predictor of G4%. CONCLUSION: Whole-lesion ADC entropy outperformed mean ADC in characterizing Gleason 7 tumors and may help refine prognosis for this heterogeneous PCa subset.

T2-weighted prostate MRI at 7 Tesla using a simplified external transmit-receive coil array: correlation with radical prostatectomy findings in two prostate cancer patients.

PURPOSE: To report design of a simplified external transmit-receive coil array for 7 Tesla (T) prostate MRI, including demonstration of the array for tumor localization using T2-weighted imaging (T2WI) at 7T before prostatectomy. MATERIALS AND METHODS: Following simulations of transmitter designs not requiring parallel transmission or radiofrequency-shimming, a coil array was constructed using loop elements, with anterior and posterior rows comprising one transmit-receive element and three receive-only elements. This coil structure was optimized using a whole-body phantom. In vivo sequence optimization was performed to optimize achieved flip angle (FA) and signal to noise ratio (SNR) in prostate. The system was evaluated in a healthy volunteer at 3T and 7T. The 7T T2WI was performed in two prostate cancer patients before prostatectomy, and localization of dominant tumors was subjectively compared with histopathological findings. Image quality was compared between 3T and 7T in these patients. RESULTS: Simulations of the B1(+) field in prostate using two-loop design showed good magnitude (B1(+) of 0.245 A/m/w(1/2)) and uniformity (nonuniformity [SD/mean] of 10.4%). In the volunteer, 90° FA was achieved in prostate using 225 v 1 ms hard-pulse (indicating good efficiency), FA maps confirmed good uniformity (14.1% nonuniformity), and SNR maps showed SNR gain of 2.1 at 7T versus 3T. In patients, 7T T2WI showed excellent visual correspondence with prostatectomy findings. 7T images demonstrated higher estimated SNR (eSNR) in benign peripheral zone (PZ) and tumor compared with 3T, but lower eSNR in fat and slight decreases in tumor-to-PZ contrast and PZ-homogeneity. CONCLUSION: We have demonstrated feasibility of a simplified external coil array for high-resolution T2-weighted prostate MRI at 7T.

Interleukin-17 promotes development of castration-resistant prostate cancer potentially through creating an immunotolerant and pro-angiogenic tumor microenvironment.

BACKGROUND: Interleukin-17 (IL-17) has been demonstrated to promote formation and growth of hormone-naïve prostate adenocarcinoma in mice. IL-17's role in development of castration-resistant prostate cancer is unknown. In the present study, we investigated IL-17's role in castration-resistant prostate cancer in a mouse model. METHODS: IL-17 receptor C (IL-17RC) deficient mice were interbred with Pten conditional mutant mice to produce RC(+) mice that maintained IL-17RC expression and RC(-) mice that were IL-17RC deficient. Male RC(+) and RC(-) mice were Pten-null and were castrated at 16 weeks of age when invasive prostate cancer had already formed. At 30 weeks of age, all male mice were analyzed for the prostate phenotypes. RESULTS: RC(-) mice displayed prostates that were smaller than RC(+) mice. Approximately 23% of prostatic glands in RC(-) mice, in contrast to 65% of prostatic glands in RC(+) mice, developed invasive adenocarcinomas. Compared to castrate RC(+) mice, castrate RC(-) mouse prostate had lower rates of cellular proliferation and higher rates of apoptosis as well as lower levels of MMP7, YBX1, MTA1, and UBE2C proteins. In addition, castrate RC(-) mouse prostate had less angiogenesis, which was associated with decreased levels of COX-2 and VEGF. Moreover, castrate RC(-) mouse prostate had fewer inflammatory cells including lymphocytes, myeloid-derived suppressor cells, and macrophages. CONCLUSIONS: Taken together, our findings suggest that IL-17 promotes development of invasive prostate adenocarcinomas under castrate conditions, potentially through creating an immunotolerant and pro-angiogenic tumor microenvironment.

Biobanking of derivatives from radical retropubic and robot-assisted laparoscopic prostatectomy tissues as part of the prostate cancer biorepository network.

BACKGROUND: The goal of the Prostate Cancer Biorepository Network (PCBN) is to develop a biorepository with high-quality, well-annotated specimens obtained in a systematic, reproducible fashion using optimized and standardized protocols, and an infrastructure to facilitate the growth of the resource and its wide usage by the prostate cancer research community. An emerging area of concern in the field of prostate cancer biobanking is an apparent shift in the proportion of surgical procedures performed for prostate cancer treatment from radical retropubic prostatectomy (RRP) to robot-assisted laparoscopic prostatectomy (RALP). Our study aimed to determine the potential impact of the RALP procedure on the detection of known prostate cancer biomarkers, and the subsequent suitability of RALP-derived specimens for prostate cancer biomarker studies. METHODS: DNA and RNA were extracted from RRP and RALP specimens. Quality assessment was conducted using spectrophotometric analysis and RNA was analyzed for RNA integrity number (RIN) and by real-time reverse-transcription PCR (qRT-PCR) for racemase, hepsin, ERG, TMPRSS2-ERG gene fusions, and the microRNAs miR-26a, miR-26b, miR-141, and miR-221. RESULTS: We demonstrate that extraction of derivatives from frozen tissues from RRP and RALP specimens yields samples of equally high quality as assessed by spectrophotometric and RIN analysis. Likewise, expression levels of genes analyzed by qRT-PCR did not differ between RRP and RALP-derived tissues. CONCLUSIONS: Our studies indicate that samples obtained from RALP specimens may be suitable for prostate cancer biomarker studies-an important finding given the current shift in surgical procedures for prostate cancer treatment.