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High-grade prostatic intraepithelial neoplasia (HGPIN) is a well-characterised precursor lesion in prostate cancer. The term atypical intraductal proliferations (AIP) describes lesions with features that are far too atypical to be considered HGPIN, yet insufficient to be diagnosed as intraductal carcinoma of the prostate (IDCP). Here, a panel of biomarkers was assessed to provide insights into the biological relationship between IDCP, HGPIN, and AIP and their relevance to current clinicopathological recommendations. Tissue samples from 86 patients with prostate cancer were assessed by routine haematoxylin and eosin staining and immunohistochemistry (IHC) with a biomarker panel (Appl1/Sortilin/Syndecan-1) and a PIN4 cocktail (34ßE12+P63/P504S). Appl1 strongly labelled atypical secretory cells, effectively visualising intraductal lesions. Sortilin labelling was moderate-to-strong in > 70% of cases, while Syndecan-1 was moderate-to-strong in micropapillary HGPIN/AIP lesions (83% cases) versus flat/tufting HGPIN (≤ 20% cases). Distinct biomarker labelling patterns for atypical intraductal lesions of the prostate were observed, including early atypical changes (flat/tufting HGPIN) and more advanced atypical changes (micropapillary HGPIN/AIP). Furthermore, the biomarker panel may be used as a tool to overcome the diagnostic uncertainty surrounding AIP by supporting a definitive diagnosis of IDCP for such lesions displaying the same biomarker pattern as cribriform IDCP.

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Purpose: The aim of our study was to observe the associations between the ETS-related gene (ERG) and the phosphatase and tensin homolog gene (PTEN) immunoexpression in prostate cancer and related lesions and highlight the clinical significance of these findings. Methods: We evaluated the immunohistochemical expression of ERG and PTEN in a series of 151 invasive prostate adenocarcinomas, including low-grade (Gleason grade pattern 3) and high-grade (Gleason grade patterns 4, 5) morphological patterns which corresponded to 45.5% and 54.4% of the cases, respectively. Additionally, we evaluated the immunoexpression of the two markers both in foci of high-grade prostatic intraepithelial neoplasia (HGPIN), as a precursor lesion of cancer, and in foci of intraductal carcinoma of the prostate (IDCP). Finally, to ensure the malignant nature of the prostate glands examined, we employed p63 and alpha-methylacyl-CoA racemase (AMACR) expression. Results: We found that PTEN loss was observed in 50.7%, and ERG positivity was detected in 41.8% of our cancerous samples. In HGPIN, PTEN loss appeared to be linked with a high-grade adjacent invasive carcinoma component which also displayed PTEN loss. As far as IDCP is concerned, ERG immunonegativity was correlated with adjacent high-grade invasive cancer, which was also ERG immunonegative. Conclusions: Our findings suggest that the clonal expansion of invasive cancer appears to be associated with distinct immunophenotypic cellular alterations of both early and late cancer-related histological lesions. Patients with PTEN loss in HGPIN in prostate biopsies should be closely monitored due to the increased likelihood of having an associated invasive high-grade carcinoma that may have not been sampled. Given the clinical significance that derives from PTEN expression in HGPIN lesions, we suggest the routine use of PTEN immunohistochemistry in prostate cancer biopsies in which HGPIN is the only finding.

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Intraductal carcinoma (IDC) of the prostate is often associated with concurrent high-grade invasive prostate cancer (PCa) and poor clinical outcomes. In this context, IDC is thought to represent the retrograde spread of invasive prostatic adenocarcinoma into the acini and ducts. Prior studies have demonstrated a concordance of PTEN loss and genomic instability between the IDC and high-grade invasive components of PCa, but larger genomic association studies to solidify our understanding of the relationship between these 2 lesions are lacking. Here, we evaluate the genomic relationship between duct-confined (high-grade prostatic intraepithelial neoplasia and IDC) and invasive components of high-grade PCa using genetic variants generated by whole exome sequencing. High-grade prostatic intraepithelial neoplasia and IDC were laser-microdissected, and PCa and nonneoplastic tissue was manually dissected from 12 radical prostatectomies. A targeted next-generation sequencing panel was used to identify disease-relevant variants. Additionally, the degree of overlap between adjacent lesions was determined by comparing exome-wide variants detected using whole exome sequencing data. Our results demonstrate that IDC and invasive high-grade PCa components show common genetic variants and copy number alterations. Hierarchical clustering of genome-wide variants suggests that in these tumors, IDC is more closely related to the high-grade invasive components of the tumor compared with high-grade prostatic intraepithelial neoplasia. In conclusion, this study reinforces the concept that, in the context of high-grade PCa, IDC likely represents a late event associated with tumor progression.

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Prostate cancer is a heterogeneous disease with a wide spectrum of pathological, clinical, and molecular features. The diagnosis and classification of prostate cancer have been constantly modified with the incorporation of new data. The 5th edition of the World Health Organization (WHO) Classification of Urinary and Genital Tumors was recently published six years after the 4th edition. In this new edition, the classification of prostate cancer has been refined in the diagnostic criteria, grading, nomenclature, and genomics. This paper reviews significant updates to the new WHO classification of prostate cancer, including high-grade prostatic intraepithelial neoplasia, acinar adenocarcinoma, intraductal carcinoma, ductal carcinoma, and neuroendocrine tumors. Controversial issues in the Gleason grading are discussed, such as intraductal carcinoma and tertiary grade. We also highlight distinct genetic and epigenetic alterations in prostate cancer that may contribute to its diverse clinicopathologic features. Overall, the 5th edition of the WHO classification provides a comprehensive assessment of prostate cancer with morphologic, immunohistochemical, genomic, and clinical data, which may represent an optimal paradigm for diagnosing and treating prostate cancer.

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"Cribriform lesions of the prostate represent an important and often diagnostically challenging spectrum of prostate pathology. These lesions range from normal anatomical variation, benign proliferative lesions, premalignant, suspicious to frankly malignant and biologically aggressive entities. The concept of cribriform prostate adenocarcinoma (CrP4) and intraductal carcinoma of the prostate (IDC-P), in particular, has evolved significantly in recent years with a growing body of evidence suggesting that the presence of these morphologies is important for clinical decision-making in prostate cancer management. Therefore, accurate recognition and reporting of CrP4 and IDC-P architecture are especially important. This review discusses a contemporary diagnostic approach to cribriform lesions of the prostate with a focus on their key morphologic features, differential diagnosis, underlying molecular alterations, clinical significance, and reporting recommendations."

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OBJECTIVE: To assess the rates of atypical small acinar proliferation (ASAP) and high-grade prostatic intraepithelial neoplasia (HGPIN) detected in prostate biopsy in China and the risk of PCa found in subsequent repeat biopsy. METHODS: A total of 2,456 patients underwent TRUS-guided prostate biopsy with the samples of ASAP and/or HGPIN tissues in our hospital at least twice between July 2014 and June 2019. We analyzed the findings of digital rectal examination, prostate volumes, PSA levels, and the results of prostate biopsies. RESULTS: Initial prostate biopsies revealed 737 cases of PCa (30.0%), 215 cases of ASAP (8.8%), 98 cases of HGPIN (4.0%), and 18 cases of ASAP+HGPIN (0.7%). Totally, 313 of the patients met the inclusion criteria and included in this study. Of the 215 cases of ASAP confirmed in the first biopsy, 72 and 25 were diagnosed with PCa in the second and third biopsies, respectively, 83 with Gleason score (GS) 6, 14 with GS7, 57 with T1c and 40 with T2a tumors. Of the 98 cases of HGPIN confirmed in the first biopsy, 1 was diagnosed with PCa in the second and another 1 in the third biopsy, both with GS6 and T1c tumors. Of the 18 cases of ASAP+HGPIN confirmed in the first biopsy, 7 and 3 were diagnosed with PCa in the second and third biopsies, respectively, 7 with GS6, 3 with GS7, 6 with T1c and 4 with T2a tumors. CONCLUSIONS: ASAP is a significant risk factor for PCa and repeat prostate biopsy should be performed for patients diagnosed with ASAP in the first biopsy. Whether repeat biopsy is necessary for those diagnosed with HGPIN depends on other related clinical parameters./.

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High-grade prostatic intraepithelial neoplasia (HGPIN) is a facultative precursor lesion of prostate cancer (PCa). Multifocal HGPIN in needle biopsies in the absence of PCa indicates a higher risk of cancer detection in subsequent biopsies. Therefore, a reliable diagnosis of HGPIN is of high clinical relevance guiding the management of patients with cancer-negative biopsies. Detection of HGPIN is merely based on morphological features while biomarkers aiding in the diagnosis of HGPIN and its differentiation from benign glands and other glandular lesions are lacking yet. Here, we investigated the expression of cyclin-dependent kinase 19 (CDK19) by immunohistochemistry on prostate needle biopsies of 140 patients who were all diagnosed with PCa using whole-tissue sections and compared CDK19 levels between HGPIN, PCa, and adjacent benign glands. In addition, CDK19 was compared with AMACR expression in a subset of intraductal carcinomas (IDCs) on radical prostatectomy (RP) specimens. HGPIN was present in 65.7% of biopsies and in 88% associated to adjacent PCa. CDK19 overexpression defined as moderate to high CDK19 expression visible at low magnification was found in 82.6% of HGPIN. In contrast, 89.3% of benign glands were CDK19-negative or demonstrated only low CDK19 expression highlighting a high sensitivity and specificity to accurately detect HGPIN based on CDK19 expression levels. CDK19 was overexpressed in 59% of PCa but did not correlate significantly with the expression of intermingled HGPIN. On RP, CDK19 and AMACR showed no significant difference in the detection rate of IDC. In summary, assessment of CDK19 facilitates accurate and simplified diagnosis of HGPIN with high sensitivity and specificity and aides the differentiation to non-neoplastic glandular alterations. Considering the high clinical significance of diagnosis HGPIN that still has a limited reproducibility among pathologists, we suggest CDK19 as diagnostic biomarker for HGPIN.

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Glyoxalase 1 (GLO1) is an enzyme involved in the detoxification of methylglyoxal (MG), a reactive oncometabolite formed in the context of energy metabolism as a result of high glycolytic flux. Prior clinical evidence has documented GLO1 upregulation in various tumor types including prostate cancer (PCa). However, GLO1 expression has not been explored in the context of PCa progression with a focus on high-grade prostatic intraepithelial neoplasia (HGPIN), a frequent precursor to invasive cancer. Here, we have evaluated GLO1 expression by immunohistochemistry in archival tumor samples from 187 PCa patients (stage 2 and 3). Immunohistochemical analysis revealed GLO1 upregulation during tumor progression, observable in HGPIN and PCa versus normal prostatic tissue. GLO1 upregulation was identified as a novel hallmark of HGPIN lesions, displaying the highest staining intensity in all clinical patient specimens. GLO1 expression correlated with intermediate-high risk Gleason grade but not with patient age, biochemical recurrence, or pathological stage. Our data identify upregulated GLO1 expression as a molecular hallmark of HGPIN lesions detectable by immunohistochemical analysis. Since current pathological assessment of HGPIN status solely depends on morphological features, GLO1 may serve as a novel diagnostic marker that identifies this precancerous lesion.

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Melanoma antigen gene A3 (MAGE-A3) is one of the most immunogenic cancer testis antigens and is common in various types of cancers. In this study, for the first time, we performed immunohistochemical analysis to evaluate the expression of MAGE-A3 in 153 prostate tissue samples including prostate cancer (PCa), benign prostatic hyperplasia (BPH), and high-grade prostatic intraepithelial neoplasia (HPIN). Increased both nuclear and cytoplasmic expression of MAGE-A3 was significantly found in PCa tissues compared with both HPIN and BPH tissues (nuclear expression at p = 0.011, and cytoplasmic expression at p = 0.034; for both comparisons p < 0.0001, respectively). A significant correlation was observed between higher nuclear and cytoplasmic expressions of MAGE-A3 with Gleason score (p < 0.0001 and 0.006, respectively). Increased expression of MAGE-A3 was associated with shorter biochemical recurrence-free survival (BCR-FS) and disease-free survival (DFS) of patients (p = 0.042 and = 0.0001, respectively). In multivariate analysis, nuclear expression of MAGE-A3 and Gleason score (≤7 vs >7) was independent predictors of the DFS (both; p = 0.019). Nuclear expression of MAGE-A3 was also significantly related to BCR-FS (p = 0.015). MAGE-A3 can be considered as a predictor for poor prognosis and an option for vaccine immunotherapy in patients with PCa.

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BACKGROUND: Melanoma antigen gene A2 (MAGE-A2) is one of the most cancer-testis antigens overexpressed in various types of cancers. Silencing the MAGE-A2 expression inhibited the proliferation of prostate cancer (PCa) cells and increased the chemosensitivity. However, the expression pattern of MAGE-A2 in PCa tissue samples and its prognostic and therapeutic values for PCa patients is still unclear. METHODS: In this study, for the first time, the staining pattern and clinical significance of MAGE-A2 were evaluated in 166 paraffin-embedded prostate tissues, including 148 cases of PCa and 18 cases of high-grade prostatic intraepithelial neoplasia (HPIN), by immunohistochemical analysis. RESULTS: The simultaneous expression of both nuclear and cytoplasmic patterns of MAGE-A2 with different staining intensities was observed among studied cases. Increased expression of MAGE-A2 was significantly found in PCa tissues compared to HPIN cases (P < 0.0001). Among PCa samples, the strong staining intensity of nuclear expression was predominantly observed in comparison with cytoplasmic expression in PCa tissues (P < 0.0001). A significant and inverse correlation was found between the cytoplasmic expression of MAGE-A2 and increased Gleason score (P = 0.002). Increased cytoplasmic expression of MAGE-A2 was associated with longer biochemical recurrence-free survival (BCR-FS) and disease-free survival (DFS) of patients (P = 0.002, P = 0.001, respectively). In multivariate analysis, Gleason score and cytoplasmic expression of MAGE-A2 were independent predictors of the BCR-FS (P = 0.014; P = 0.028, respectively). CONCLUSIONS: Taken together, cytoplasmic expression of MAGE-A2 was inversely proportional to the malignant grade and duration of recurrence of the disease in patients with PCa.

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Objective@#To assess the rates of atypical small acinar proliferation (ASAP) and high-grade prostatic intraepithelial neoplasia (HGPIN) detected in prostate biopsy in China and the risk of PCa found in subsequent repeat biopsy.@*METHODS@#A total of 2,456 patients underwent TRUS-guided prostate biopsy with the samples of ASAP and/or HGPIN tissues in our hospital at least twice between July 2014 and June 2019. We analyzed the findings of digital rectal examination, prostate volumes, PSA levels, and the results of prostate biopsies.@*RESULTS@#Initial prostate biopsies revealed 737 cases of PCa (30.0%), 215 cases of ASAP (8.8%), 98 cases of HGPIN (4.0%), and 18 cases of ASAP+HGPIN (0.7%). Totally, 313 of the patients met the inclusion criteria and included in this study. Of the 215 cases of ASAP confirmed in the first biopsy, 72 and 25 were diagnosed with PCa in the second and third biopsies, respectively, 83 with Gleason score (GS) 6, 14 with GS7, 57 with T1c and 40 with T2a tumors. Of the 98 cases of HGPIN confirmed in the first biopsy, 1 was diagnosed with PCa in the second and another 1 in the third biopsy, both with GS6 and T1c tumors. Of the 18 cases of ASAP+HGPIN confirmed in the first biopsy, 7 and 3 were diagnosed with PCa in the second and third biopsies, respectively, 7 with GS6, 3 with GS7, 6 with T1c and 4 with T2a tumors.@*CONCLUSIONS@#ASAP is a significant risk factor for PCa and repeat prostate biopsy should be performed for patients diagnosed with ASAP in the first biopsy. Whether repeat biopsy is necessary for those diagnosed with HGPIN depends on other related clinical parameters./.

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OBJECTIVE: To assess the current ability of atypical small acinar proliferation (ASAP), multifocal high-grade prostatic intraepithelial neoplasia (mHGPIN), HGPIN with atypia (PINATYP) and other non-malignant lesions to predict clinically significant prostate cancer (csPCa) in repeat prostate biopsies. METHODS: This retrospective study analyzed 377 repeat prostate biopsies, carried out between 2.014 and 2.017, and excluding those with previous PCa or 5-alpha reductase inhibitors treatment. ASAP, mHGPIN, PINATYP, prostatic atrophy, prostatic hyperplastic atrophy, proliferative inflammatory atrophy (PIA), chronic prostatitis, acute prostatitis, or granulomatous prostatitis, were prospectively reported after 12-core transrectal ultrasound (TRUS) systematic negative previous biopsies. 3T-multiparametric magnetic resonance imaging (mpMRI) was performed previous repeat biopsies. At least 2-core TRUS targeted biopsies of Prostate Imaging-Reporting and Data Systemv2 lesions ≥3, and/or 12-core TRUS systematic biopsy were performed in repeat prostate biopsies. The main outcome measurements were csPCa detection, which was defined when the International Society of Uro-Pathology group grade >1 and avoided biopsies. After logistic regression analysis the most efficient model was selected, nomogram was designed with internal validation, and clinical utility was analyzed. RESULTS: Normal benign tissue alone was present in less than 2% of previous negative biopsies. mHGPIN (39.7%), ASAP (4.3%) and PINATYP (3.7%) failed to predict csPCa risk in repeat biopsies. The finding of PIA (38.2%) associated with a decreased the risk of csPCa with an Odd ratio of 0.54 (95% confidence interval: 0.31-0.95), P= 0.031. The area under the curve, to predict csPCa, of mpMRI was 0.736, increasing up to 0.860 (95% confidence internal:0.82-0.90) when PSA density, age, digital rectal examination, and differential PSA between biopsies and PIA finding were integrated in a predictive model. At 6% threshold, more than 20% of repeat prostate biopsies were saved without missing csPCa. CONCLUSION: Currently, mHGPIN in negative prostate biopsy seems not able to predict the risk of future csPCa. The low incidence of ASAP and PINATYP, in our series, did not allow us to draw conclusions. PIA finding associated with a reduced risk of csPCa, and it could be integrated in a useful based-mpMRI predictive nomogram.

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@#CIP2A is an oncoprotein involved in the progression of several human malignancies. It has recently been described as a prognostic marker in many cancers. The present study aimed to investigate the immunohistochemical expression of CIP2A in benign prostatic hyperplasia (BPH), high grade prostatic intraepithelial neoplasia (HGPIN) and prostate cancer (PC), and to analyse the association with the clinicopathological parameters in PC cases to define its role in the development and progression of PC. Materials and Methods: Immunohistochemical staining for CIP2A was performed on the tissue microarray sections of 105 PC, 27 HGPIN and 27 BPH tissues. The CIP2A expression scores were compared with several clinicopathological parameters. Results: CIP2A was expressed in 96,2% of PC, 55,6% of HGPIN and 40,7% of BPH tissues. The expression of CIP2A in PC was significantly higher than in HGPIN (p<0.0001) and BPH (p<0.0001) cases. CIP2A expression score was significantly associated with Gleason score (p=0.032) and lymphovascular invasion (p=0.039). Nevertheless, there was no statistically significant association between the expression of CIP2A and perineural invasion, pT stage, metastasis and recurrence (p>0.05). Multivariate analysis indicated that GS, lymphovascular invasion, distant metastasis were independent prognostic factors for PC patients but, CIP2A expression score was not found to be a prognostic factor. Additionally, there was no significant difference between the survival times of patients according to CIP2A expression (p=0.174). Conclusion: According to our results, the expression of CIP2A protein is increased in PC and its expression may be involved in the development, differentiation, and aggressiveness of PC. However, further studies are needed to confirm our findings and to clarify the role of CIP2A in the development of PC.

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Background: High-grade prostatic intraepithelial neoplasia (HGPIN) is the most likely precancerous lesion for prostatic adenocarcinoma (PCa). Recent molecular studies have shown that HGPIN can harbor TMPRSS2-ERG fusion, a genetic marker also associated with PCa, which may provide an additional risk stratification tool for HGPIN, especially when present as an isolated lesion. Our aim was to assess the frequency of HGPIN and ERG expression in a cohort of prostatic needle core biopsies from Jordanian-Arab patients with PCa. Materials and methods: We studied 109 needle core biopsies from patients with PCa. Clinical data, including age and preoperative prostate specific antigen (PSA) level, were obtained from patients' medical records. Results: HGPIN was present in 31 (28.4 %) of the 109 cases. Of the HGPIN cases, 13 (41.9%) expressed ERG immunostain. ERG expression in HGPIN was independent of patient age at presentation (P=0.4), pre-operative PSA (P=0.9), and the grade, using the novel Grade Groups (P=0.5). Conclusion: The frequency of HGPIN in our cohort appears similar to the one found in the Western patient populations and demonstrates a comparable frequency of ERG expression in these lesions.

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INTRODUCTION: In cases of persistent suspicion of prostate cancer (PC), repeat prostate biopsies (PB) are frequently performed in spite of their low yield. In the context of a negative PB, there is a microscopic scenario (MS), which we define as the group of recognizable non-neoplastic lesions. While some of these lesions seem to have a protective effect, the existence of others increases the risk of PC detection in posterior PB. The objective of this systematic review is to identify the lesions that may belong to the MS of a negative PB and analyse the current evidence of their association with the risk of detecting PC in subsequent PBs. EVIDENCE ACQUISITION: Two independent reviewers conducted a literature search on Medline, Embase and Central Cochrane with the following search terms: small acinar proliferation, ASAP, prostatic intraepithelial neoplasia, HGPIN, adjacent small atypical glands, pinatyp, atrophy, proliferative inflammatory atrophy, pia, prostatic inflammation, prostatitis and prostate cancer. 1,015 references were first identified, and 57 original articles were included in the study, following the PRISMA declaration and the PICO selection principles. EVIDENCE SYNTHESIS: Atypical small acinar proliferation is associated with PC detection in repeat PB with rates ranging between 32 and 48%. High-grade prostatic intraepithelial neoplasia (HGPIN) is related to PC in 13 to 42% of cases. Studies show that HGPIN, when multifocal, is a significant independent risk factor for PC. Prostatic atrophy, inflammatory proliferative atrophy and prostatic inflammation seem to act as protective factors on the detection of PC in repeat PB. On the other hand, the risk of PC detection reduces significantly in male patients with multifocal HGPIN and coexistent PIA. CONCLUSIONS: The MS of a negative PB may include atypical small acinar proliferation, HGPIN, prostatic atrophy, inflammatory proliferative atrophy and prostatic inflammation lesions, since they all seem to be associated with the risk of PC detection in repeat PB. This review has led us to create the hypothesis that the MS of a negative PB might be a valuable and useful tool when considering repeat PB.

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In vitro experiments demonstrated that stimulation of Toll-like receptor 9 (TLR-9) by synthetic TLR-9 ligands induces the invasion of TLR-9-expressing prostate cancer cells through matrix metalloproteinase 13 (MMP-13). However, the clinical value of TLR-9 and MMP-13 co-expression in the pathophysiology of the prostate is unknown. In the study, we evaluated the expression levels and clinical significance of the TLR-9 and MMP-13 in a series of prostate tissues. One hundred and eighty prostate tissues including prostate cancer (PCa) (n = 137), high-grade prostatic intraepithelial neoplasia (HPIN) (n = 18) and benign prostatic hyperplasia (BPH) (n = 25) were immunostained for the TLR-9 and MMP-13 markers. Subsequently, the correlation between the TLR-9 and MMP-13 staining scores and clinicopathological parameters was obtained. Higher expressions of TLR-9 and MMP-13 were found in PCa and high-grade prostatic intraepithelial neoplasia compared to benign prostatic hyperplasia tissues. Among PCa samples, a positive relationship was revealed between the MMP-13 expression and Gleason score (P < 0.001). There was a significant correlation between TLR-9 expression and regional lymph node involvement (P = 0.04). The expression patterns of TLR-9 and MMP-13 markers demonstrated a reciprocal significant correlation between the two markers in the same series of prostate samples (P < 0.001). Furthermore, the Gleason score of TLR-9high /MMP-13high and TLR-9low /MMP-13low phenotypes showed a significant difference (P = 0.002). Higher expressions of TLR-9 and MMP-13 can confer aggressive behaviour to PCa. Therefore, these markers may be used as a valuable target for tailored therapy of PCa.

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Atypical adenomatous hyperplasia (AAH) of the prostate is characterized by lobular proliferation of closely packed small acini. It is hypothesized that AAH is a precursor lesion for low-grade prostate cancer arising from the transition zone. Telomere dysfunction is common during malignant transformation of epithelia. In this study, we investigate telomere shortening in AAH (n = 93), high-grade prostatic intraepithelial neoplasia (HGPIN) ( n = 68), and prostatic adenocarcinoma (PCA) ( n = 70) using quantitative fluorescence in situ hybridization. Twenty percent (19 of 93) of AAH specimens, 68% (46 of 68) of HGPIN, and 83% (58 of 70) of PCA showed significant telomere shortening. Thirty-two percent of AAH lesions had α-methylacyl-CoA racemase (AMACR) expression, a sensitive and specific marker for HGPIN and PCA. AMACR expression in AAH was seen more frequently in AAH foci with telomere shortening or coexisting PCA. Our findings indicate that a subset of AAH lesions have telomere shortening and AMACR expression, suggesting that these foci may be precursors for PCA.

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INTRODUCTION AND OBJECTIVES: To evaluate the association between metabolic syndrome (MetS) and proliferative inflammatory atrophy (PIA) in patients with suspected prostate cancer (PCa). PATIENTS AND METHODS: From June 2015 to July 2016, we conducted the FIERY (Flogosis Increased Events of pRostatic biopsY) study at the Urology section, Department of Surgery of the University of Catania (Local registration number: #131/2015). A total of 205 patients with elevated prostate-specific antigen (≥ 4 ng/ml) or clinical suspicion of PCa who underwent primary transperineal prostate biopsy were included in this cross-sectional study. The assessment of PIA, HGPIN, and PCa were performed by 2 experienced pathologists and samples were investigated for the presence of an inflammatory infiltrate, according to the Irani score. Primary and secondary Gleason grade of tumor in positive biopsies were evaluated according to the 2016 ISUP Modified Gleason System. RESULTS: In the entire cohort, median age was 68.0 (interquartile range: 62.0-74.5), median prostate-specific antigen was 6.5 (interquartile range: 5.51-9.57). The prevalence of MetS was 34.1%, the detection rate of PCa was 32.7%, the rate of PIA was 28.3%, the rate of HGPIN was 32.2%, whereas the rate of severe intraprostatic inflammation (Irani-score ≥4) was 28.8%. When comparing clinical and histological variables in patients without and with PIA, metabolic aberrations where not significantly different in both groups. We did not find statistical association in detection rate of PCa (29.3% vs. 34.0%; P = 0.07) and HGPIN (27.6% vs. 34.0%; P = 0.37) in patients with and without PIA, respectively. When considering metabolic aberrations, MetS was not associated with Irani-score ≥4 (28.6% vs. 28.4%; P = 0.96) and none of each component was statistically predictive of severe inflammation. At the multivariable logistic regression analysis, PIA, HGPIN, and MetS were not associated with greater risk of PCa. CONCLUSION: In this study, we did not show an association between MetS and PIA and PCa. Although the small sample size and the cross-sectional nature of the study, we do not suppose that MetS could be associated with greater evidence of PIA. Further studies should be conducted to evaluate the exact nature of this pathological lesion.

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INTRODUCTION: Atypical small acinar proliferation (ASAP) and high grade prostatic intraepithelial neoplasia (HGPIN) are considered precancerous. We aimed to measure the rate of repeat biopsy and adenocarcinoma in patients with ASAP and HGPIN and identify any clinico-pathologic parameters at diagnosis of ASAP/HGPIN that are predictive of adenocarcinoma. MATERIALS AND METHODS: Patients with a diagnosis of ASAP/HGPIN with no previous or concomitant cancer were identified. Prostate specific antigen (PSA) and magnetic resonance imaging (MRI) changes were monitored. Re-biopsy was at clinician discretion. RESULTS: Nineteen were diagnosed with ASAP and 17 with HGPIN. Seven with ASAP (37%) and 6 with HGPIN (35%) underwent re-biopsy. Three (16%) with ASAP and 5 with HGPIN (29%) were diagnosed with adenocarcinoma. The difference in cancer detection rates between ASAP and HGPIN was not significant (p = 0.35). Five (14%) in total required definitive therapy for adenocarcinoma. Twenty-three (64%) did not undergo repeat biopsy. Parameters at diagnosis of HGPIN and ASAP, including PSA, prostate volume and PSA density, were compared between the cancer and non-cancer cohorts with none found to be predictive of adenocarcinoma. CONCLUSION: By monitoring PSA and MRI changes, we managed to spare re-biopsy in two-thirds of patients. Further evaluation is necessary to characterize a surveillance protocol in these populations.

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INTRODUCTION: In recent years there has been an increasing interest in the drug treatment of benign prostatic hyperplasia (BPH) to improve the patients quality of life without surgical treatment. In this connection, phytotherapeutic drugs and biologically active dietary supplements (BADS), consisting of a combination of microelements, vitamins and plant extracts, have been increasingly used in addition to synthetic preparations. OBJECTIVE: To investigate the clinical effectiveness of dietary supplement ProstaDoz in the treatment of BPH with coexistent high-grade prostatic intraepithelial neoplasia (PIN). MATERIALS AND METHODS: The study group comprised 30 men with BPH and high-grade PIN who were diagnosed with primary biopsy and received ProstaDoz for three months. The control group included 18 patients with the same diagnosis who were treated with Tamsulosin. RESULTS: After a 3-month intake of the ProstaDoz, a statistically significant reduction was observed in symptom scores for BPH and the quality of life index by 18% (p<0.001) and 16.7% (p<0.001), respectively. The residual urine volume and total serum PSA decreased by 28.3% (p<0.001) and 46.8% (p<0.001), respectively. Unlike the control group, the rate of prostate cancer detection was 6.25 times lower in patients taking ProstaDoz, and 16% of them had lower grade PIN compared with baseline or no PIN at all. CONCLUSION: The findings suggest that using ProstaDoz in patients with BPH and high-grade PIN contributes to improving the quality of life (QoL) of patients and the regression of dysplasia.

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