Increased expression of YAP1 in prostate cancer correlates with extraprostatic extension.

Objective:Yes associated protein 1 (YAP1) is a member of the Hippo pathway, acting as a transcriptional coactivator. To elucidate the role of YAP1 and phosphorylated (p)YAP1 in prostate cancer (PCa) tumorigenesis, we investigated their expression in clinical samples of PCa and cell lines. Methods:Fifty-four tumor, adjacent nontumor, and prostate intraepithelial neoplasia (PIN) tissues from patients with PCa after radical prostatectomy were selected from a retrospective cohort and studied using immunohistochemistry (IHC). Protein and mRNA expression levels of YAP1 were evaluated by Western blot analysis and quantitative real-time reverse transcription PCR, respectively, in cancer cell lines. Publicly available gene expression datasets were downloaded to analyze YAP1 mRNA and protein levels in PCa tissue samples. Results:IHC analysis of PCa tissues revealed that YAP1 staining intensities were moderate to weak in the nucleus and cytoplasm of tumor cells, whereas adjacent normal epithelia showed strong staining. We observed that benign prostates were characterized by higher expression levels of both nuclear (P=0.004) and cytosolic (P=0.005) YAP1. pYAP1 staining was weak in the cytoplasm and absent in the nucleus of all the tissues investigated. YAP1 expression was an indicator of extraprostatic extension (EPE). The level of YAP1 was negatively correlated with the level of the androgen receptor (AR) in The Cancer Genome Atlas dataset and Western blot analysis of cell lines. Conclusions:Our study suggested that YAP1 expression is heterogeneous in PCa tissue samples; therefore, YAP1 might play different roles in different aspects of PCa progression. This might involve AR-YAP1 interplay in PCa

根治的前立腺全摘標本における神経線維周囲浸潤の生化学的再発予知因子としての意義

著者らは, 臨床的限局性前立腺癌に対して術前内分泌療法を施行せずに根治的前立腺全摘除術を施行した202症例を対象に, 全摘標本における神経線維周囲浸潤の臨床病理学的意義を検討した.その結果, 1)神経線維周囲浸潤は131例(64.9%)に陽性であった.また, 神経線維周囲浸潤の存在は, 臨床病期, 病理学的病期, Gleasonスコア, 精嚢浸潤, リンパ節転移および腫瘍体積と有意に相関したが, 術前PSA値との相関は認めなかった. 2)経過観察期間(中央値34ヵ月)中, 20例に生化学的再発を認めたが神経線維周囲浸潤はこの内17例に陽性であった. 3)神経線維周囲浸潤陽性131例および陰性71例の5年生化学的非再発率は, それぞれ84.4%および94.3%であり統計学的有意差を認めた.神経線維周囲浸潤の他, 病理学的病期, 精嚢浸潤, リンパ節転移および腫瘍体積が生化学的非再発率と有意な相関を示した.しかし, 多変量解析の結果, これら5因子の内, 精嚢浸潤のみが生化学的再発の独立した予知因子であった.以上, これらのことからも, 根治的前立腺全摘標本における神経線維周囲浸潤の存在は, 種々の予後規定因子と有意な相関を示すが, 生化学的再発の独立した予知因子とは成りえない可能性が示唆されたThe objective of this study was to determine whether the presence of perineural invasion (PNI) in radical prostatectomy specimens could be a useful prognostic parameter in Japanese men with prostate cancer. Between January 1995 and September 2003, 202 Japanese men underwent radical retropubic prostatectomy for prostate cancer without any neoadjuvant therapies prior to surgery. We retrospectively analyzed the relationship between PNI in radical prostatectomy specimens and other prognostic factors, and also assessed the significance of PNI in biochemical recurrence after radical prostatectomy. The presence of PNI was significantly related to clinical stage, pathological stage, Gleason score, seminal vesicle invasion, lymph node metastasis and tumor volume, but not pretreatment serum prostate specific antigen value. During the observation period, biochemical recurrence occurred in 20 patients (3 in patients without PNI and 17 in those with PNI), and the biochemical recurrence-free survival rate in patients with PNI was significantly lower than that in patients without PNI. In addition to-PNI, pathological stage, seminal vesicle invasion, lymph node metastasis and tumor volume were significantly associated with the biochemical recurrence-free survival rate; however, among these five factors, only seminal vesicle invasion was an independent predictor of biochemical recurrence on multivariate analysis. Despite a significant association between several prognostic parameters, PNI was not an independent predictor of biochemical recurrence; therefore, it may not provide an additive effect to consider the presence of PNI in predicting the prognosis of Japanese men who underwent radical prostatectomy if there are other conventional parameters available

Multiparametric magnetic resonance imaging of the prostate-a basic tutorial.

Prostate cancer is the second most common cause of cancer related death in the United States and the most commonly diagnosed malignancy in men. In general, prostate cancer is slow growing, though there is a broad spectrum of disease that may be indolent, or aggressive and rapidly progressive. Screening for prostate is controversial and complicated by lack of specificity and over diagnosis of clinically insignificant cancer. Imaging has played a role in diagnosis of prostate cancer, primarily through systemic transrectal ultrasound (TRUS) guided biopsy. While TRUS guided biopsy radically changed prostate cancer diagnosis, it still remains limited by low resolution, poor tissue characterization, relatively low sensitivity and positive predictive value. Advances in multiparametric magnetic resonance imaging (mpMRI) have allowed more accurate detection, localization, and staging as well as aiding in the role of active surveillance (AS). The use of mpMRI for the evaluation of prostate cancer has increased dramatically and this trend is likely to continue as the technique is rapidly improving and its applications expand. The purpose of this article is to review the basic principles of mpMRI of the prostate and its clinical applications, which will be reviewed in greater detail in subsequent chapters of this issue

African American men with low-grade prostate cancer have increased disease recurrence after prostatectomy compared with Caucasian men.

PURPOSE: To explore whether disparities in outcomes exist between African American (AA) and Caucasian (CS) men with low-grade prostate cancer and similar cancer of the prostate risk assessment-postsurgery (CAPRA-S) features following prostatectomy (RP). METHODS: The overall cohort consisted of 1,265 men (234 AA and 1,031 CS) who met the National comprehensive cancer network criteria for low- to intermediate-risk prostate cancer and underwent RP between 1990 and 2012. We first evaluated whether clinical factors were associated with adverse pathologic outcomes and freedom from biochemical failure (FFbF) using the entire cohort. Next, we studied a subset of 705 men (112 AA and 593 CS) who had pathologic Gleason score≤6 (low-grade disease). Using this cohort, we determined whether race affected FFbF in men with RP-proven low-grade disease and similar CAPRA-S scores. RESULTS: With a median follow-up time of 27 months, the overall 7-year FFbF rate was 86% vs. 79% in CS and AA men, respectively (P = 0.035). There was no significant difference in one or more adverse pathologic features between CS vs. AA men (27% vs. 31%; P = 0.35) or CAPRA-S score (P = 0.28). In the subset analysis of patients with low-grade disease, AA race was associated with worse FFbF outcomes (P = 0.002). Furthermore, AA race was a significant predictor of FFbF in men with low-grade disease (hazard ratio = 2.01, 95% CI: 1.08-3.72; P = 0.029). CONCLUSIONS: AA race is a predictor of worse FFbF outcomes in men with low-grade disease after RP. These results suggest that a subset of AA men with low-grade disease may benefit from more aggressive treatment

Prognostic Histopathological and Molecular Markers on Prostate Cancer Needle-Biopsies: A Review

Prostate cancer is diverse in clinical presentation, histopathological tumor growth patterns, and survival. Therefore, individual assessment of a tumor's aggressive potential is crucial for clinical decision-making in men with prostate cancer. To date a large number of prognostic markers for prostate cancer have been described, most of them based on radical prostatectomy specimens. However, in order to affect clinical decision-making, validation of respective markers in pretreatment diagnostic needle-biopsies is essential. Here, we discuss established and promising histopathological and molecular parameters in diagnostic needle-biopsies

Impact of the SPOP Mutant Subtype on the Interpretation of Clinical Parameters in Prostate Cancer.

Purpose: Molecular characterization of prostate cancer, including The Cancer Genome Atlas, has revealed distinct subtypes with underlying genomic alterations. One of these core subtypes, SPOP (speckle-type POZ protein) mutant prostate cancer, has previously only been identifiable via DNA sequencing, which has made the impact on prognosis and routinely used risk stratification parameters unclear. Methods: We have developed a novel gene expression signature, classifier (Subclass Predictor Based on Transcriptional Data), and decision tree to predict the SPOP mutant subclass from RNA gene expression data and classify common prostate cancer molecular subtypes. We then validated and further interrogated the association of prostate cancer molecular subtypes with pathologic and clinical outcomes in retrospective and prospective cohorts of 8,158 patients. Results: The subclass predictor based on transcriptional data model showed high sensitivity and specificity in multiple cohorts across both RNA sequencing and microarray gene expression platforms. We predicted approximately 8% to 9% of cases to be SPOP mutant from both retrospective and prospective cohorts. We found that the SPOP mutant subclass was associated with lower frequency of positive margins, extraprostatic extension, and seminal vesicle invasion at prostatectomy; however, SPOP mutant cancers were associated with higher pretreatment serum prostate-specific antigen (PSA). The association between SPOP mutant status and higher PSA level was validated in three independent cohorts. Despite high pretreatment PSA, the SPOP mutant subtype was associated with a favorable prognosis with improved metastasis-free survival, particularly in patients with high-risk preoperative PSA levels. Conclusion: Using a novel gene expression model and a decision tree algorithm to define prostate cancer molecular subclasses, we found that the SPOP mutant subclass is associated with higher preoperative PSA, less adverse pathologic features, and favorable prognosis. These findings suggest a paradigm in which the interpretation of common risk stratification parameters, particularly PSA, may be influenced by the underlying molecular subtype of prostate cancer

Does prostate acinar adenocarcinoma with Gleason Score 3 + 3 = 6 have the potential to metastasize?

Background: There is a worldwide debate involving clinicians, uropathologists as well as patients and their families on whether Gleason score 6 adenocarcinoma should be labelled as cancer. Case description: We report a case of man diagnosed with biopsy Gleason score 6 acinar adenocarcinoma and classified as low risk (based on a PSA of 5 ng/mL and stage cT2a) whose radical prostatectomy specimen initially showed organ confined Gleason score 3 + 3 = 6, WHO nuclear grade 3, acinar adenocarcinoma with lymphovascular invasion and secondary deposit in a periprostatic lymph node. When deeper sections were cut to the point that almost all the slice present in the paraffin block was sectioned, a small tumor area (<5% of the whole tumor) of Gleason pattern 4 (poorly formed glands) was found in an extraprostatic position. Conclusion: The epilogue was that the additional finding changed the final Gleason score to 3 + 3 = 6 with tertiary pattern 4 and the stage to pT3a. Virtual Slides: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/ vs/13000_2014_19

Renal dysplasia with the ipsilateral ectopic ureter mimicking abscess of the prostate

Introduction. In males the ectopic ureter usualy drains into the prostate (50%). During ureteric developement a thin membrane (Chawalla’s membrane) separates the lumen of the ureter and the urogenital sinus at the point where the ureter joins the urogenital sinus. This membrane ruptures allowing urin to drain from the ureter to the urogenital sinus. The authors reported a case of renal dysplasia associated with ipsilateral uretral ectopia mimicking prostatic abscess. Case report. A subfebrile (37.3°C), 23-year-old patient, otherwise healthy, presented with persistent ascending perineal pain non-responsive to antibiotics and analgetics. Digitorectal examination (DRE) showed asymmetric prostate with a soft, tender, buldging left lobe suggestive of prostatic abscess. The diagnosis was suspected using transrectal ultrasonography (TRUS), but the picture of the anechoic tubular structure in the left lobe of the prostate with a proximal undefined extraprostatic extension and a caudal intraprostatic blind end was incoclusive for the definitive diagnosis of prostatic abscess. Magnetic resonance imaging (MRI) was ordered and definitive diagnosis of renal dysplasia associated with the ipsilateral ectopic ureter filled with inflamed content mimicking prostatic abscess was made. Transurethral incision/minimal resection of the distal, blindly closed end of left ectopic ureter was done. Endoscopic surgical treatment was sufficient for relief of clinical symptoms. The patient’s recovery was uneventful. Conclusion. To the best of our knowledge, a case of renal dysplasia with the ipsilateral ectopic ureter mimicking prostate abscess has not been reported so far. Cystic pelvic malformations in males may result from too craniall sprouting of the ureteral bud, with delayed absorption and ectopic opening of the distal end of the ureter