Prostatic Intraepithelial Neoplasia Research Articles

LIM domain kinase 1

Background Despite recent advancement, prostate cancer (PC) remains to represent a leading cause of cancer mortality and morbidity in men. Diagnosis of PC faces many challenges, especially on core biopsies. Multiple signaling pathways have been involved in PC progression. However, castration resistance eventually develops, especially in metastatic PC. Identifying a marker that helps in distinguishing invasive tumor from benign and precursor lesions, as well as predicts its metastatic and prognostic potentials, is needed. LIM-domain kinase 1 (LIMK1) is a newly identified marker that affects the cytoskeleton of cancer cells. Its role in PC is still not well understood. This study aimed at evaluating LIMK1 expression in benign prostatic hyperplasia (30 cases), high-grade prostatic intraepithelial neoplasia (27 cases), and PC prostatic adenocarcinoma (60 cases) and its association with the prognostic clinicopathological parameters in PC. Results No strong expression was detected in benign prostatic hyperplasia expression compared with 25.9% and 48.3% in high-grade prostatic intraepithelial neoplasia and prostatic adenocarcinoma (Pca) groups. The expression was statistically higher in the Pca group than the other groups. There was significant association with poor prognostic parameters in Pca groups, including higher prostate-specific antigen levels, tumor percentage, Gleason scores, grade groups, T stage, positive lymph-node metastases, extracapsular extension, seminal vesicle invasion, distant metastasis, and prognostic-stage group. Conclusion LIMK1 is considered a promising diagnostic and prognostic marker in Pca.

Status of Mast Cells in Autopsy Specimens of Prostate: A Cross-sectional Study

Introduction: Mast cells are found in areas rich in connective tissues and beneath epithelial surfaces. Mast cells have been extensively studied for their orchestration of allergic reactions and autoimmunity. Mast cells infiltrate various prostatic lesions in varying concentrations. Autopsy specimens had not been investigated extensively in the previous literature. Aim: To find out a quantitative estimation of mast cells and the association of the number of mast cells in various prostatic lesions that included both inflammatory and neoplastic lesions in autopsy cases. Materials and Methods: A cross-sectional, analytical study was carried out in the Department of Pathology, R.G. Kar Medical College and Hospital, Kolkata, India from April 2017 to March 2018. Sixty autopsy specimens of the prostate were dissected from the deceased males above 30 years of age. Four to six paraffin embedded sections from different lobes and peri-urethral areas were taken. Haematoxylin and Eosin (H&E) stained sections for histopathological diagnosis and toluidine-blue stain after water mounting to demonstrate mast cells by its metachromasia were performed. Mast cell densities were estimated by a light microscope under high power magnification (400X) on an average of 100 fields. Gross and microscopic findings were recorded. Data analysis correlation was done using Statistical Package for the Social Sciences (SPSS) software version 18.0. Mean and standard deviations were determined for different prostatic lesions. Group means were compared using the student’s t-test. For statistical significance p-value of less than 0.05 was considered. Results: A total of 60 autopsy specimens of the prostate were studied comprising 8 (13.5%) specimens of normal prostate, which acted as a control, 6 (10%) specimens of prostatitis, 27 (45%) specimens of Benign Hypertrophy of Prostate (BHP), 12 (20%) specimens of BHP with Prostatic Intraepithelial Neoplasia (PIN), 3 (5%) specimens of prostatitis with focal PIN and 4 (6.5%) specimens of prostatic adenocarcinoma. Mast Cell Density (MCD) was higher in prostatitis {6-8 per High Power Fields (HPF)}, compared to normal (1-3/HPF) and BHP (3-5/ HPF), lowest in adenocarcinoma (1-2/HPF) and intermediate in PIN (2-4/HPF). Conclusion: Mast cell density was the lowest in prostatic adenocarcinoma and significantly higher in prostatitis, probably due to a lack of antitumour immunity in higher grades, whereas it was significantly higher in chronic non specific prostatitis possibly because of inflammatory response.

Abstract PO-102: Multifocal analysis of the ETS (-) subtypes, mutated SPOP and overexpression of SPINK-1, in prostate cancer from Colombian patients as a process of understanding the carcinogenesis model of the disease

Abstract The Cancer Genome Atlas (TCGA) Research Network defined the SPOP-mutant subset of prostate cancers (PCa) had frequent overexpression of SPINK1 mRNA, which suggests a relationship in these subtypes that had not been evaluated simultaneously in other studies on ETS(-) subtypes as a key feature in the molecular taxonomy of prostate cancer. However, this analysis was performed on the index tumors and it is suggested that a better knowledge of the different molecular profiles of different neoplastic foci, in the same prostate, could be affecting the relationship of the molecular subtypes and prognosis of the disease. With an approximate 50% prevalence of ETS family gene fusions, attempts to molecularly characterize PCa often begin with the division into ETS(-) and ETS (+). To represent the molecular heterogeneity of PCa, which could improve medical decision-making, we aim to study it through the expression of SPINK-1 and mutations in SPOP; as well as the TMPRSS2-ERG fusion status, in order to assess the clonality of the foci in each patient and also the possible association of this alteration with different degrees of differentiation and lymph node metastasis. FFPE samples of different foci with different lesion degrees: High-Grade Prostatic Intraepithelial Neoplasia (n=17), PCa foci with different Gleason scores (n= 53; GL3: (n=23); GL4: (n=23) and GL5: (n=7)), and positive lymph node (LN) (n=13) from radical prostatectomy from twenty patients were used to analyse the presence of TMPRSS2-ERG fusion and expression levels of ERG and SPINK-1 using RT-PCR. Sanger sequencing was used in exon 6 and 7 to analyze mutations in SPOP. The molecular concordance between the different prostatic foci of the same patient was determined, taking into account subclonal events. The LN were compared with prostatic foci to try to establish its clonal origin. The results indicate that multifocal PCa may have monoclonal or multiclonal origin. SPINK-1 overexpression was the predominant pattern in the LN, while the opposite was the most frequent in the HGPIN samples. None of the thirteen analyzed LN showed the same pattern of other PCa foci from each patient. Metastasis have less molecular heterogeneity than pre-neoplastic lesions. The ERG(+) subtype was found in 54.7% of the foci and 70% of the patients. No mutations were found in SPOP. The frequency of overexpressed SPINK-1 in the 20 patients was 60%. In this study, the frequency of SPINK-1 cases overexpressed in ERG(-) taking into account all the samples analyzed as independent, even if they were from the same patient, due to the high heterogeneity in PCa, coincides with that expected (11%), but it should be taken into account that the foci that tested positive did not show total exclusivity with ERG(+), and in fact, there were more associated with it (74%), which does not agree with what was found in other studies that had not taken into account samples of patients from our country, which highlights the importance of personalized medicine and of not extrapolating results from other populations in our population. Citation Format: Yenifer Y. Segura Moreno, María C. Sanabria Salas, Jorge A. Mesa López De Mesa, Rodolfo Varela Ramirez, Natalia L. Acosta Vega, Martha L. Serrano López. Multifocal analysis of the ETS (-) subtypes, mutated SPOP and overexpression of SPINK-1, in prostate cancer from Colombian patients as a process of understanding the carcinogenesis model of the disease [abstract]. In: Proceedings of the AACR Virtual Conference: 14th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2021 Oct 6-8. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr PO-102.

Prostate Intraepithelial Neoplasia in Prostate Core Biopsies done for Suspected Prostate Cancer

Prostate Intraepithelial Neoplasia in Prostate Core Biopsies done for Suspected Prostate Cancer

Prostate Biopsies and its Correlation with Prostate Specific Antigen in Patients Attending Birat Medical College Teaching Hospital, Morang, Nepal

INTRODUCTION: Prostate cancer is the most common malignant tumor in men over the age of 65 years. It is the second most common cause of cancer related death in men after lung cancer but it can be completely cured if detected at an early stage. Most frequently encountered diseases of the prostate are benign prostatic hyperplasia, prostatitis and carcinoma. Increased prostate specific antigen levels are found to be closely associated with prostate cancer. It is a tumour marker which is a glycoprotein and is expressed by both normal and neoplastic prostate tissue. This study was done to determine the correlation between histopathological diagnosis in prostatic biopsy and serum prostatic specific antigen level. 
 MATERIALS AND METHODS: This is a hospital based cross sectional study carried out in the Department of Pathology, Birat Medical College Teaching Hospital from February 15, 2020 to October 15, 2020. A total of 84 cases were included in this study. All representative tissue sections were taken, paraffin embedded blocks were prepared and stained with hematoxylin and eosin stain. Histopathological examination was done and it’s association with serum prostatic specific antigen level was observed. 
 RESULTS: In the biopsy findings, Benign Prostatic Hyperplasia (BPH) was the most common case seen in 41 (48.8%) cases out of 84 cases with maximum incidence seen in 60-69 years age group (13 cases). A total of 10 (11.9%) cases were those of prostatic adenocarcinoma and were seen in the 70-79 years age group. Majority of benign cases (BPH and BPH with prostatitis) were seen in the PSA range of 0-7ng/ml. Maximum cases of Prostatic Intraepithelial Neoplasia (PIN) were seen in the PSA range of 0-7 or 7.1-14 ng/ml and adenocarcinoma in the range of >20ng/ml. The finding showed that adenocarcinoma is associated with increased level of serum PSA level. 
 CONCLUSIONS: PSA is a specific marker for prostatic tissue. It can be raised in benign lesions of the prostate due to membrane disruption. However, an increased PSA level above 20 ng/ml increases the chance of detecting malignant lesions.

Correlation between Prostate Specific Antigen (PSA) Level and Various Prostatic Diseases on Biopsies: A Retrospective Study

Introduction: The prostate is a pear-shaped glandular organ that adds part of fluid to semen. The prostate consists of stromal and glandular components. Prostate needle biopsy is performed either transrectal ultrasound (TRUS) guided or transurethral routes. PSA is a glycoprotein produced by secretory cells. Normally the PSA levels are less than 4.0ng/ml.
 Aim: The main aim of the study is to find out the correlation between various pathological lesions occur in the prostate and serum Prostate Specific Antigen (PSA) level.
 Study Design: A retrospective study.
 Place and Duration of Study: Department of Pathology,Saveetha Medical college and Hospital, between January 2019 and December 2019.
 Methodology: A retrospective study of 84 prostatic biopsies for a period of 1 year in the year 2019 was carried out. All specimens subjected for histopathological examination and the relevant clinical data and Serum PSA values correlation was done.
 Results: Commonest age group being 61-70 years. Difficulty in micturition was the most common presentation .Most common lesion found was Benign Prostatic Hypertrophy(BPH) constituting 67 cases (71.42%) followed by BPH with prostatitis 17 cases (20.23%), adenocarcinoma 6 cases (7.14%) and 1 case of Prostatic Intraepithelial Neoplasia (PIN) (1.19%). BPH patients, had S.PSA levels in the range of 4.1-15 ng/ml. Three cases of adenocarcinoma showed very high levels of S.PSA (>100 ng/ml) with the Gleason score of 9(5+4).
 Conclusion: Both benign and malignant pathologies can cause an increase in serum PSA levels, but the chances of finding malignancy increases with rising values of PSA. But in the management of prostatic cancer the histopathological diagnosis and grading plays a definitive role.

High-intensity interval training attenuates the effects caused by arterial hypertension in the ventral prostate.

The prostatic effects induced by arterial hypertension is very controversial and its mechanism is unclear. High-intensity interval training (HIIT) is an exercise considered to be hypotensive. The objective of this work was to investigate the molecular, biochemical, and morphological effects of 8 weeks of HIIT in the prostatic tissue of spontaneously hypertensive rats (SHR). Twenty male SHR rats, 51.4 weeks old, were used. The SHR animals were divided into two groups: spontaneously sedentary hypertensive and spontaneously hypertensive submitted to HIIT. We analyze androgens receptor and glucocorticoid receptors in the prostate. Still, we verify effects of the hypertension and HIIT on the physiopathology prostatic, for immunohistochemistry investigated BCL-2, BAX, IGF-1, FAS/CD95, data's inflammatory tumour necrosis factor α, nuclear factor kappa B and interleukin (IL)-6, anti-inflammatory IL-10. The echocardiographic evaluation was performed at the baseline and after the training period. Arterial hypertension promote high prostatic intraepithelial neoplasia incidence in the prostate, increases IGF-1, BCL-2 (p < 0.05), and inflammatory proteins (p < 0.05). Eight weeks of HIIT training reduced the arterial pressure and increase the concentration of tissue collagen and intracellular glycogen and showed a higher expression of BAX, FAS/CD95, and IL-10 proteins (p < 0.05), coinciding with a lower incidence of lesions and lower prostate weight (p < 0.05) and reduction of the BCL-2 and IGF-1. Our data suggested that arterial hypertension suppressed apoptosis and increased damage prostatic. On other hand, HIIT promotes morphology and function improves in the prostatic environment, inhibited inflammation, and increased apoptosis.

P2X4 purinergic receptors offer a therapeutic target for aggressive prostate cancer.

Prostate cancer (PCa) remains a leading cause of cancer-related deaths in American men and treatment options for metastatic PCa are limited. There is a critical need to identify new mechanisms that contribute to PCa progression, that distinguish benign from lethal disease, and that have potential for therapeutic targeting. P2X4 belongs to the P2 purinergic receptor family that is commonly upregulated in cancer and is associated with poorer outcomes. We observed P2X4 protein expression primarily in epithelial cells of the prostate, a subset of CD66+ neutrophils, and most CD68+ macrophages. Our analysis of tissue microarrays representing 491 PCa cases demonstrated significantly elevated P2X4 expression in cancer- compared with benign-tissue spots, in prostatic intraepithelial neoplasia, and in PCa with ERG positivity or with PTEN loss. High-level P2X4 expression in benign tissues was likewise associated with the development of metastasis after radical prostatectomy. Treatment with the P2X4-specific agonist cytidine 5'-triphosphate (CTP) increased Transwell migration and invasion of PC3, DU145, and CWR22Rv1 PCa cells. The P2X4 antagonist 5-(3-bromophenyl)-1,3-dihydro-2H-benzofuro[3,2-e]-1,4-diazepin-2-one (5-BDBD) resulted in a dose-dependent decrease in viability of PC3, DU145, LNCaP, CWR22Rv1, TRAMP-C2, Myc-CaP, BMPC1, and BMPC2 cells and decreased DU145 cell migration and invasion. Knockdown of P2X4 attenuated growth, migration, and invasion of PCa cells. Finally, knockdown of P2X4 in Myc-CaP cells resulted in significantly attenuated subcutaneous allograft growth in FVB/NJ mice. Collectively, these data strongly support a role for the P2X4 purinergic receptor in PCa aggressiveness and identify P2X4 as a candidate for therapeutic targeting. © 2021 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Implications of a diagnosis of atypical small acinar proliferation (ASAP) and high-grade prostatic intraepithelial neoplasia (HGPIN) on prostate biopsy: a 5-year follow-up study.

In the era of active surveillance of low- and intermediate-risk prostatic cancer, a reconsideration of the implications of a biopsy report of ASAP and/or HGPIN may be timely. We investigated the implications of a diagnosis of atypical small acinar proliferation (ASAP) and high-grade prostatic intraepithelial neoplasia (HGPIN) on prostate biopsy. The rate of re-biopsy and the incidence of carcinoma on repeat biopsy for benign, HGPIN, and ASAP groups were compared. Mean PSA and PSA velocity was also compared between groups. There was an increased risk of developing prostate cancer in the following 5years with a biopsy diagnosis of ASAP compared to benign (20% vs 5.9%, p = 0.009), and with a biopsy of HGPIN compared with benign (14.8% vs 5.9%, p = 0.005). The frequency of repeat biopsy following a diagnosis of ASAP (54.2%) vs. HGPIN (37%) was not significantly different (p = 0.079). The risk of developing prostate cancer was highest following a biopsy with concomitant ASAP and HGPIN compared to benign (50% vs 5.9%, p < 0.001). There was no significant difference in PSA values between the 3 diagnostic groups at the time of initial biopsy (p = 0.206). The findings of this study suggest that a biopsy diagnosis of ASAP ± HGPIN, on either initial or surveillance biopsy, provides support for earlier repeat mpMRI and/or re-biopsy. This may assist in directing to early re-biopsy those patients likely to have intermediate- and high-risk prostate cancer.

COMPARISON OF BASAL-CELL SPECIFIC MARKERS – P63 AND 34BETAE12 IN PROSTATIC GLANDULAR PROLIFERATIONS

Background: The prostate is a retroperitoneal organ encircling the neck of the bladder and urethra. Though the diagnosis of the prostatic lesions are analyzed through histopathological examination (HPE), sometimes, diagnosis can be challenging, when pathologist are faced with certain problems such as small foci of Ca or benign mimickers. In such situation, immunohistochemical (IHC) detection of basal cells are widely used. To Objectives: assess the expression of basal cell markers (p63 and 34betaE12) in various prostatic glandular proliferations and to differentiate suspicious glandular lesions as benign or malignant. A two year cross-sectional s Methods: tudy (Sept'2016 –Aug'2018) , total of 52 cases of both TURP and prostate biopsy specimens sent to the department of Pathology, RIMS for HPE were studied using IHC markers p63 and 34betaE12, following H&amp;E stain and the expressions of the markers were studied. Results: Out of 52 cases, 41(78.8%) cases were diagnosed as Benign proliferative hyperplasia (BPH), 8(15.4%) cases as prostatic carcinoma, 2(3.8%) cases as high grade prostatic intraepithelial neoplasia (HGPIN) and one (1.9%) case of adenoleiomyobromatous hyperplasia (AMFH) on H&amp;E section with age range of 51 to 90 years (mean age: 72 years). Following IHC staining, 43 (97.7%) benign cases were positive for both p63 and 34betaE12, one (2.3%) case of benign lesion was negative for both the IHCs. 8(100%) cases of malignant lesions were negative for both the IHCs. A p-value of 1.000 was observed indicating that there is no signicant difference in the sensitivity of p63 and 34betaE12. In this cross- Conclusion: sectional study of 52 cases of prostatic lesions, HPE and the role of basal cell specic IHC markers p63 and 34beta12 were studied. No signicant difference was observed in the sensitivity between the two markers. Further comparative study with larger sample size is needed to comprehend the differences in the utility of p63 and 34etaE12 in diagnosing suspicious prostatic lesions.

Dimensional reduction based on peak fitting of Raman micro spectroscopy data improves detection of prostate cancer in tissue specimens.

.Significance: Prostate cancer is the most common cancer among men. An accurate diagnosis of its severity at detection plays a major role in improving their survival. Recently, machine learning models using biomarkers identified from Raman micro-spectroscopy discriminated intraductal carcinoma of the prostate (IDC-P) from cancer tissue with a detection accuracy and differentiated high-grade prostatic intraepithelial neoplasia (HGPIN) from IDC-P with a accuracy.Aim: To improve the classification performance of machine learning models identifying different types of prostate cancer tissue using a new dimensional reduction technique.Approach: A radial basis function (RBF) kernel support vector machine (SVM) model was trained on Raman spectra of prostate tissue from a 272-patient cohort (Centre hospitalier de l’Université de Montréal, CHUM) and tested on two independent cohorts of 76 patients [University Health Network (UHN)] and 135 patients (Centre hospitalier universitaire de Québec-Université Laval, CHUQc-UL). Two types of engineered features were used. Individual intensity features, i.e., Raman signal intensity measured at particular wavelengths and novel Raman spectra fitted peak features consisting of peak heights and widths.Results: Combining engineered features improved classification performance for the three aforementioned classification tasks. The improvements for IDC-P/cancer classification for the UHN and CHUQc-UL testing sets in accuracy, sensitivity, specificity, and area under the curve (AUC) are (numbers in parenthesis are associated with the CHUQc-UL testing set): (), (), (6%), () with respect to the current best models. Discrimination between HGPIN and IDC-P was also improved in both testing cohorts: (), (), (), (). While no global improvements were obtained for the normal versus cancer classification task [ (), (), (), ()], the AUC was improved in both testing sets.Conclusions: Combining individual intensity features and novel Raman fitted peak features, improved the classification performance on two independent and multicenter testing sets in comparison to using only individual intensity features.

Galactose specific lectins from prostate tissue with different pathologies: biochemical and cellular studies.

Galectins-galactose-specific lectins are involved in various types of cell activities, including apoptosis, cell cycle regulation, inflammation and cell transformation. Galectins are implicated in prostate malignat transformation. It is not known yet if prostate glands with different grade of pathologies are expressing different galectins and if these galectins express different effects on the cell viability. Cytosolic galactose-spesific lectin fractions from prostate tissue with different diagnosis were purified by affinity chromatography and analyzed by electrophoresis in polyacrylamide gel electrophoresis with sodium dodecyl sulphate. The lectin effects in a source-dependent maner were studied on cell viability on peripheral lymphocytes by MTT reduction method and on apoptosis by flow cytometry method. Affinity purified galactose-specific lectins fractions from normal and pathological tissue samples are characterized with different protein composition and they express different effects on cell viability and apoptosis. The effects of cytosolic galactose-specific lectins depend on the source of lectin fraction (glandular tissue disease). We suppose that the released cytosolic galectins from prostatic high grade intraepithelial neoplasia and adenocarcinoma tissue could suppress the immune status of the host patients.

Identification of prostate cancer using multiparametric MR imaging characteristics of prostate tissues referenced to whole mount histopathology

In this study, the objective was to characterize the MR signatures of the various benign prostate tissues and to differentiate them from cancer. Data was from seventy prostate cancer patients who underwent multiparametric MRI (mpMRI) and subsequent prostatectomy. The scans included T2-weighted imaging (T2W), diffusion weighted imaging, dynamic contrast-enhanced MRI (DCE MRI), and MR spectroscopic imaging. Histopathology tissue information was translated to MRI images. The mpMRI parameters were characterized separately per zone and by tissue type. The tissues were ordered according to trends in tissue parameter means. The peripheral zone tissue order was cystic atrophy, high grade prostatic intraepithelial neoplasia (HGPIN), normal, atrophy, inflammation, and cancer. Decreasing values for tissue order were exhibited by ADC (1.8 10−3 mm2/s to 1.2 10−3 mm2/s) and T2W intensity (3447 to 2576). Increasing values occurred for DCE MRI peak (143% to 157%), DCE MRI slope (101%/min to 169%/min), fractional anisotropy (FA) (0.16 to 0.19), choline (7.2 to 12.2), and choline / citrate (0.3 to 0.9). The transition zone tissue order was cystic atrophy, mixed benign prostatic hyperplasia (BPH), normal, atrophy, inflammation, stroma, anterior fibromuscular stroma, and cancer. Decreasing values occurred for ADC (1.6 10−3 mm2/s to 1.1 10−3 mm2/s) and T2W intensity (2863 to 2001). Increasing values occurred for DCE MRI peak (143% to 150%), DCE MRI slope (101%/min to 137%/min), FA (0.18 to 0.25), choline (7.9 to 11.7), and choline / citrate (0.3 to 0.7). Logistic regression was used to create parameter model fits to differentiate cancer from benign prostate tissues. The fits achieved AUCs ≥0.91. This study quantified the mpMRI characteristics of benign prostate tissues and demonstrated the capability of mpMRI to discriminate among benign as well as cancer tissues, potentially aiding future discrimination of cancer from benign confounders.

MP26-10 CORRELATION OF WHOLE-MOUNT HISTOLOGY WITH FALSE POSITIVES PROSTATE IMAGING REPORTING AND DATA SYSTEMS VERSION 2 CATEGORY 4 AND 5 LESIONS

You have accessJournal of UrologyProstate Cancer: Detection & Screening II (MP26)1 Sep 2021MP26-10 CORRELATION OF WHOLE-MOUNT HISTOLOGY WITH FALSE POSITIVES PROSTATE IMAGING REPORTING AND DATA SYSTEMS VERSION 2 CATEGORY 4 AND 5 LESIONS Yu Xi Terence Law, Edwin Jonathan Aslim, Stephanie Man Chung Fook-Chong, Henry Sun Sien Ho, John Shyi Peng Yuen, Weber Kam On Lau, Lui Shiong Lee, Christopher Wai Sam Cheng, Nye Thane Ngo, Yan Mee Law, and Kae Jack Tay Yu Xi Terence LawYu Xi Terence Law More articles by this author , Edwin Jonathan AslimEdwin Jonathan Aslim More articles by this author , Stephanie Man Chung Fook-ChongStephanie Man Chung Fook-Chong More articles by this author , Henry Sun Sien HoHenry Sun Sien Ho More articles by this author , John Shyi Peng YuenJohn Shyi Peng Yuen More articles by this author , Weber Kam On LauWeber Kam On Lau More articles by this author , Lui Shiong LeeLui Shiong Lee More articles by this author , Christopher Wai Sam ChengChristopher Wai Sam Cheng More articles by this author , Nye Thane NgoNye Thane Ngo More articles by this author , Yan Mee LawYan Mee Law More articles by this author , and Kae Jack TayKae Jack Tay More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002023.10AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: To describe the radiological, clinical and histological features associated with Prostate Imaging Reporting and Date Systems version2 (PIRADsv2) category 4 and 5 lesions that were found to be benign on whole-mount histology. METHODS: We identified men with organ confined prostate cancer who had multiparametric MRI of the prostate performed before primary radical prostatectomy. The MRI images were retrospectively reassessed to identify and grade suspicious lesions. Those of PIRADSv2 categories 4 and 5 were correlated with wholemount histology, classifying the lesions as benign, high grade (Gleason score (GS) 4-5) or low grade (GS 3) prostate cancer. Multivariate logistic regression was used to identify clinical or radiological factors associated with benign histology. RESULTS: There were 128 PIRADSv2 4/5 lesions detected on MRI in 64 patients. On histology, 22.7% (29/128) were benign, 18.0% (23/128) were low-grade (G3) cancer and 59.3% (76/128) were high-grade (GS 4/5) cancer. In 72 PIRADSv2 4 lesions, 20 lesions (28%) are benign, while in 56 PIRADSv2 5 lesions, 9 lesions (16%) are benign. Factors associated with benign pathology at multivariate analysis were lower prostate specific antigen density (PSAD) (Odds ratio (OR) 0.04; p=0.025), smaller volume of MRI lesions (OR 0.93; p=0.041) and posterior location (OR 3.13; p=0.017). The benign histological findings included benign prostate hyperplasia, inflammation (acute, chronic and granulomatous), atrophic glands and high grade prostatic intraepithelial neoplasia. CONCLUSIONS: There is a significant degree of false positive rates with multiparametric MRI for prostate in its current form. Further refinement in techniques, perhaps incorporating certain predictive factors, may improve the diagnostic accuracy for prostate cancer detection. Source of Funding: N.A. © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e466-e466 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Yu Xi Terence Law More articles by this author Edwin Jonathan Aslim More articles by this author Stephanie Man Chung Fook-Chong More articles by this author Henry Sun Sien Ho More articles by this author John Shyi Peng Yuen More articles by this author Weber Kam On Lau More articles by this author Lui Shiong Lee More articles by this author Christopher Wai Sam Cheng More articles by this author Nye Thane Ngo More articles by this author Yan Mee Law More articles by this author Kae Jack Tay More articles by this author Expand All Advertisement Loading ...

MP33-12 THE POTENTIAL ROLE OF CTLH COMPLEX IN THE PROSTATE CANCER

You have accessJournal of UrologyProstate Cancer: Basic Research & Pathophysiology I (MP33)1 Sep 2021MP33-12 THE POTENTIAL ROLE OF CTLH COMPLEX IN THE PROSTATE CANCER Mario Scarpa, Marta De Menna, Eugenio Zoni, Sofia Karkampouna, and Marianna Kruithof-de Julio Mario ScarpaMario Scarpa More articles by this author , Marta De MennaMarta De Menna More articles by this author , Eugenio ZoniEugenio Zoni More articles by this author , Sofia KarkampounaSofia Karkampouna More articles by this author , and Marianna Kruithof-de JulioMarianna Kruithof-de Julio More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002042.12AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Prostate cancer (PCa) is the most frequent malignancy detected in men and the second leading cause of cancer-related male death in Europe. Current markers frequently fail in providing an effective patient stratification. Unfortunately, lethal cases receive new therapies only when they have failed local and hormonal treatment. This project is focused on the role, in PCa progression, of Ran Binding Protein 9 (RanBP9), a key component of the mammalian macromolecular complex CTLH E3-ubiquitin ligase. This complex is characterized by well conserved CTLH domain and in DU145 cell lines its ubiquitin ligase activity increases cell radiosensitivity. All these evidences suggest that the CTLH Complex, through RanBP9, is potentially involved in the PCa tumorigenesis. METHODS: To elucidate the biological mechanism and function of CTLH in the PCa, we performed in vitro analyses using prostate cancer cell lines as: PC3, LNCaP and C42B. To study the role of the CTLH complex in vivo we are using PDXs BM18 (androgen dependent), LAPC9 (androgen-independent) and GEMM for PCa: Nkx3.1CreERT2/+; Pten flox/flox; R26LSL-YFP (NP) and Nkx3.1CreERT2/+; Pten flox/flox; KRas LSLG12D/+; R26 LSL-YFP (NPK). In particular NP and NPK animals mimic different stages of PCa tumorigenesis. After tamoxifen treatment NP animals will develop high grade PIN lesions while the NPK animals will develop prostate adenocarcinoma with lung and liver metastasis. RESULTS: The levels of RanBP9 were measured on a TMA (Tissue Micro Array) of 201 High-Risk PCa patients. It revealed that higher levels of RanBP9 was associated with PSA progression. Also, in the TMA cells expressing NKX3.1 were low compare a higher number of cells expressing RanBP9. In the GEMM models NP and NPK, RanBP9 expression is higher in the more aggressive phenotype (NP primary vs NPK primary and metastasis). Interesting, the level of RanBP9 expression were particularly higher in NPK metastasis vs NPK primary. RanBP9 levels were measured in PDXs LAPC9 and BM18 in both intact and castrated setting. Interestingly, levels of RanBP9 in both PDXs model were affected by castration. Currently, to further explore the relationship between RanBP9 and the AR axis we are generating RanBP9-KD stable clones in PC3 (AR-) and LNCaP (AR+) cell lines. CONCLUSIONS: Our results suggested that RanBP9 expression is correlated with PCa progression. The modulation of the RanBP9 expression is probably regulated by the presence of testosterone due its downregulation following castration beyond the androgen-dependent or -independent profile of PCa. Source of Funding: KFS 4960-02-2020 © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e611-e611 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Mario Scarpa More articles by this author Marta De Menna More articles by this author Eugenio Zoni More articles by this author Sofia Karkampouna More articles by this author Marianna Kruithof-de Julio More articles by this author Expand All Advertisement Loading ...

The current recommendation for the management of isolated high-grade prostatic intraepithelial neoplasia.

To analyse the current predictive value of isolated high-grade prostatic intraepithelial neoplasia (HGPIN) for clinically significant prostate cancer (csPCa) detection in repeat biopsies. A cohort of 293 men with isolated HGPIN detected in previous biopsies performed without multiparametric magnetic resonance imaging (mpMRI), and who underwent repeat biopsy within 1 to 3 years, was analysed. Pre-repeat biopsy mpMRI and guided biopsies to suspicious lesions (Prostate Imaging - Reporting and Data System [PI-RADS] ≥3) and/or and systematic biopsies were performed. Persistent prostate cancer (PCa) suspicion, defined as sustained serum prostate-specific antigen level >4 ng/mL and/or abnormal digital rectal examination, was present in 248 men (84.6%), and was absent in 45 men (15.4%). A control group of 190 men who had no previous HGPIN, atypical small acinar proliferation or HGPIN with atypia who were scheduled to undergo repeat biopsy due to persistent PCa suspicion were also analysed. csPCa was defined as tumours of Grade Group ≥2. In the subset of 45 men with isolated HGPIN, in whom PCa suspicion disappeared, only one csPCa (2.2%) and one insignificant PCa (iPCa) were detected. csPCa was detected in 34.7% of men with persistent PCa suspicion and previous HGPIN, and in 28.4% of those without previous HGPIN (P =0.180). iPCa was detected in 12.1% and 6.3%, respectively (P =0.039). Logistic regression analysis showed that the risk of csPCa detection was not predicted by previous HGPIN: odds ratio (OR) 1.369 (95% confidence interval [CI] 0.894-2.095; P =0.149); however, previous HGPIN increased the risk of iPCa detection: OR 2.043 (95% CI 1.016-4.109; P =0.006). The risk of csPCa in men with isolated HGPIN, in whom PCa suspicion disappears, is extremely low. Moreover, in those men in whom PCa suspicion persists, the risk of csPCa is not influenced by the previous finding of HGPIN. However, previous HGPIN increases the risk of iPCa detection. Therefore, repeat prostate biopsy should not be recommended solely because of a previous HGPIN.

A STUDY TO CORRELATE HISTOPATHOLOGY, SERUM PSA LEVEL AND IMMUNOHISTOCHEMICAL EXPRESSION OF ER & PR IN PROSTATIC GROWTH

Objectives- Prostate is a bromusculoglandular structure situated at the neck of urinary bladder. It enlarges due to benign hyperplasia of prostate (BHP), prostatic intraepithelial neoplasia (PIN) or adenocarcinoma. Enlargement of prostate is associated with raised serum level of prostate-specic antigen (PSA) and altered expression of estrogen receptor (ER) and progesterone receptor (PR). The aim of our study is to correlate the histopathology, PSA levels and altered expression of ER and PR by immunohistochemistry in different prostatic growth lesions. Methodology- Patients diagnosed as having prostatic growth were enrolled and their serum PSA levels were noted. Histopathological examination and immunohistochemical analysis of prostatic tissues for ER and PR were carried out to nd out correlation of different type of growth with serum PSA level and expression of ER and PR. Results- A total 96 cases studied of them 61(63.54%) patients presented with BHP, 20(20.83%) patients with BHP with chronic prostatitis, 3 patients presented with metaplastic changes, 5 cases with of PIN and 6 patients presented with adenocarcinoma with different Gleason score. PR expression positivity in epithelial cells and stromal cells of BHP cases were 51(83.6%) and 53(86.88%) respectively. Patients presented with adenocarcinoma showed only 33.33 %( 2cases) positivity in epithelial cells and 50% (3cases) positivity in stromal cells. Serum PSA level were signicantly higher in adenocarcinoma patients as compare to BHP patients. Conclusion- By observing these ndings it can be suggested that and antiprogesterone therapy may be helpful in the treatment of prostatic adenocarcinoma.

CDK19 as a diagnostic marker for high-grade prostatic intraepithelial neoplasia

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 sectionsand 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.

Analysis of Saliva Lipids in Breast and Prostate Cancer by IR Spectroscopy.

We have developed a method for studying the lipid profile of saliva, combining preliminary extraction and IR spectroscopic detection. The case–control study involved patients with a histologically verified diagnosis of breast and prostate cancer and healthy volunteers. The comparison group included patients with non-malignant pathologies of the breast (fibroadenomas) and prostate gland (prostatic intraepithelial neoplasia). Saliva was used as a material for biochemical studies. It has been shown that the lipid profile of saliva depends on gender, and for males it also depends on the age group. In cancer pathologies, the lipid profile changes significantly and also depends on gender and age characteristics. The ratio of 1458/1396 cm−1 for both breast and prostate cancer has a potential diagnostic value. In both cases, this ratio decreases compared to healthy controls. For prostate cancer, the ratio of 2923/2957 cm−1 is also potentially informative, which grows against the background of prostate pathologies. It is noted that, in all cases, changes in the proposed ratios are more pronounced in the early stages of diseases, which increases the relevance of their study in biomedical applications.

Glyoxalase 1 Expression as a Novel Diagnostic Marker of High-Grade Prostatic Intraepithelial Neoplasia in Prostate Cancer.

Simple SummaryProstate cancer (PCa) is the most commonly diagnosed cancer and the second leading cause of cancer-associated deaths in men in the USA. Glyoxalase 1 (GLO1) is an enzyme involved in energy metabolism in various tumor types including 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 tumor samples from a PCa patient cohort. Immunohistochemical analysis indicated that GLO1 is upregulated during tumor progression, observable in HGPIN and PCa as compared to normal prostatic tissue. Remarkably, GLO1 upregulation was identified as a hallmark of HGPIN lesions, displaying the highest staining intensity in all clinical patient specimens. Since current pathological assessment of HGPIN status solely depends on morphological features, GLO1 may serve as a novel diagnostic marker that identifies these precancerous lesions.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.