Prostate Specimens Research Articles

ROLE OF EXPRESSION OF P63 AND CALPONIN IN PROSTATIC BIOPSIES

Background: An increased number of mortality and morbidity in elderly men is caused due to prostatic diseases all over the world. An increase in mass screening programmes conducted with the help of Prostate Specic Antigen (PSA) blood test along with Digital rectal examination (DRE) and imaging studies has resulted in an upsurge in the diagnosis of prostatic cancer which is markedly noted in the recent decades. Material And Methods: A total 100 cases of formalin xed parafn embedded histological sections of various prostatic lesions including benign prostatic hyperplasia, prostatic intraepithelial lesion and prostate carcinoma were studied. Out of 100 cases, 55 cases were benign prostatic hyperplasia, 10 cases of prostatic intraepithelial lesion and 35 cases were of prostate adenocarcinoma. All the sections were stained with Hematoxylin and Eosin stain and then immunohistochemical staining of p63 and Calponin was performed on all the cases (gure 6- 12). The parameters used to analyse the expression of both p63 and calponin were - Pattern of staining, Percentage of stained cell, Intensity of staining reaction. Total 100 cases i Results: ncluded in this study, out of which 55 (55%) cases were benign prostatic hyperplasia, 10 (10%) cases of prostatic intraepithelial neoplasia, and 35 (35%) cases were prostatic adenocarcinoma, majority of specimens (78%) were TURP followed by trucut biopsy (20%), Suprapubic prostatectomy (2%). The proportion of Transurethral resection of prostate (TURP) was signicantly higher as compared to the proportion of Trucut biopsy and supra pubic prostatectomy (SPP) (p<.001). Expression of calponin in various prostatic lesion. On analysing expression of proliferation marker calponin, in BPH it was expressed in only 52 cases out of 5 cases (94.5%) and 3 cases (8.6%) were negative. Our study concluded that the proportion of Benign prostatic Conclusion: hyperplasia was signicantly higher as compared to the Prostatic intraepithelial neoplasia and Prostatic adenocarcinoma. Immunohistochemical staining by p63 is diagnostically reliable in identifying basal cells in prostatic needle biopsies and TURP specimens. p63 is a valuable tool with high sensitivity in differentiating BPH from prostatic carcinoma. The decreased or absent stromal staining of calponin which indicates a reactive stroma in malignancy can be used alone or in conjunction with p63 for conrmation of diagnosis of prostatic carcinoma

Detection of high-risk Human Papillomavirus in prostate cancer from a UK based population

Human papillomavirus (HPV) infection is one of the sexually transmitted diseases which have been implicated in the etiology of multiple cancers. To date, several studies have been conducted to evaluate the incidence of high-risk (HR) HPV in prostate cancer (PCa) which have generated widely conflicting data. Hence, this leaves a lack of awareness on the causal role of persistent HPV infection in the development of PCa. Although this has been investigated in a handful of countries, to the best of our knowledge, no prior studies have been conducted in the UK. In this study, polymerase chain reaction (PCR) and Sanger sequencing were implemented to analyze a total of 49 fresh prostate specimens (35 benign and 14 malignant specimens) for the presence of viral DNA of 12 HR-HPV types. Data obtained confirmed the presence of HR-HPV in 32.7% of analyzed benign and malignant prostate tissues with HPV 35 being identified as the most frequent type. Moreover, HR-HPV positivity rate was found to be higher in abnormal prostate tissues (adenocarcinoma and benign with prostatitis) compared those with normal prostate condition. Using immunohistochemistry, we have confirmed the expression of HPV E7 protein in prostate tissues positive for HPV DNA. This observation, the first reported from a UK population, suggests that the presence of HPV in prostate tissue is likely to be a related factor in the progression of certain cases of prostate cancer.

Single-Port Robotic Transvesical Simple Prostatectomy Step by Step

We detail the instruments required to perform a single-port robotic transvesical simple prostatectomy, as well as the surgical technique to perform this operation using the single-port robot. A 3-cm transverse incision is made three fingerbreadths above the pubic symphysis and a longitudinal cystotomy is made. The roll wound retractor rolling ring is inserted into the bladder lumen, with the access port, SP Short Entry Guide, and AirSeal trocar within it. The robot is then docked to the SP cannula, and the bladder is insufflated to 8 mm Hg. A semilunar incision is made through the bladder mucosa using the monopolar scissors along the posterior aspect of the bladder neck or median lobe. The forceps can be used to retract the prostatic adenoma, while using the monopolar scissors to further bluntly dissect the adenoma from the capsule. The prostatic adenoma can be removed en bloc, but is usually removed en lobe. A vesicourethral mucosal advancement flap is performed with 3-0 V-Loc suture from apex to base at 3-o-clock and 9-o-clock; a double-arm 3-0 V-Loc suture is then used to approximate the bladder and urethral mucosa, by running from 6-o-clock to 12-o-clock. Prostatic adenoma specimens can be removed from the SP Access Port directly or removed from the bladder using the robotic camera for observation. The cystotomy is closed in two layers with 3-0 Vicryl suture. The patient is observed for 2 hours on continuous bladder irrigation to determine ambulatory discharge eligibility. Follow-up is in 3 to 7 days for trial of void. Disclosure: Portions of this video and title were presented at the AUA 2023 in the form of a video abstract and as an AUA Core Curriculum video. https://www.auajournals.org/doi/pdf/10.1097/JU.0000000000003288.06 Patient Consent Statement: Authors have received and archived patient consent for video recording/publication in advance of video recording of procedure. There are no commercial associations during the past 3 years that might create a conflict of interest in connection with the video. Runtime of video: 7 mins 37 secs

PD21-09 GENOMIC ALTERATIONS IN UNITED STATES VETERANS WITH METASTATIC PROSTATE CANCER AND SELF-REPORTED AGENT ORANGE EXPOSURE

You have accessJournal of UrologyCME1 Apr 2023PD21-09 GENOMIC ALTERATIONS IN UNITED STATES VETERANS WITH METASTATIC PROSTATE CANCER AND SELF-REPORTED AGENT ORANGE EXPOSURE JJ Zhang, Adam Weiner, Lorna Kwan, Sara Ahmed, Michael Kelley, Karim Chamie, Kara Maxwell, and Isla Garraway JJ ZhangJJ Zhang More articles by this author , Adam WeinerAdam Weiner More articles by this author , Lorna KwanLorna Kwan More articles by this author , Sara AhmedSara Ahmed More articles by this author , Michael KelleyMichael Kelley More articles by this author , Karim ChamieKarim Chamie More articles by this author , Kara MaxwellKara Maxwell More articles by this author , and Isla GarrawayIsla Garraway More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003287.09AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Agent Orange has been posited as an environmental risk factor for prostate cancer among United States Veterans. Prior studies have shown that Veterans with Agent Orange exposure are diagnosed at a younger age and at more advanced clinical stages. It is unknown if there are differences in somatic alterations among Veterans exposed to Agent Orange. METHODS: Genomic alterations were identified from clinical tumor testing conducted from 2019–2022 in a large cohort of Veterans with metastatic prostate cancer diagnosed from 2001–2022. Primary prostate and metastatic carcinoma tissue specimens were submitted for Foundation Medicine tumor-only sequencing. Baseline demographics, clinical, and genomic alterations data were stratified by Veteran self-reported exposure to Agent Orange in accordance with an Institutional Review Board approved protocol. RESULTS: Of the 2673 Veterans with metastatic prostate cancer who underwent tumor-only genomic testing, 629 reported exposure to Agent Orange (23.5%) and 2044 were not exposed. TMPRSS2-ERG fusions were more frequent in men who reported exposure to Agent Orange (35.1% vs 28.8%, p<0.01). Agent Orange exposure also correlated to higher rates of androgen receptor (AR) alterations (12.4% vs 9.5%, p=0.04) and FGFR1/2/3/4 alterations (3.3% vs 1.7%, p=0.01). On multivariable analysis, alterations in AR (OR 1.43, p=0.02), and FGFR1/2/3/4 (OR 1.84, p=0.03) remained more frequent in Veterans exposed to Agent Orange. As expected, age at prostate cancer diagnosis (OR 0.98, p<0.001) and Black/African-American race (OR 0.33, p<0.001) were associated with decreased odds of TMPRSS2-ERG alterations. In addition, current smoking status (OR 1.43, p=0.01) and rural environment (OR 1.33, p<0.01) were also associated with increased odds of a TMPRSS2-ERG fusion. There were no significant differences in alterations by Agent Orange exposure in TP53, CDK12, ERBB2, EGFR, BRCA, and genes implicated in the DNA damage response and repair (DDR), mismatch repair (MMR), and PTEN/PI3K/AKT pathways. CONCLUSIONS: Agent Orange exposure may contribute to tumor genomic alterations in AR and FGFR in prostate cancer. These findings hold potential prognostic and therapeutic implications for U.S. Veterans with metastatic prostate cancer. Source of Funding: NIH (K08CA215312, KNM; 5P50CA092131, R01 PAR-20-077, IPG); US DOD (W81XWH211075, IPG) Prostate Cancer Foundation (PCF17CHAL04, IPG; 20YOUNG02, KNM), Burroughs Wellcome Foundation (1017184, KNM); Basser Center for BRCA at UPENN (KNM); Jean Perkins Foundation (IPG), STOP Cancer Foundation (IPG) © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e593 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information JJ Zhang More articles by this author Adam Weiner More articles by this author Lorna Kwan More articles by this author Sara Ahmed More articles by this author Michael Kelley More articles by this author Karim Chamie More articles by this author Kara Maxwell More articles by this author Isla Garraway More articles by this author Expand All Advertisement PDF downloadLoading ...

PD02-10 THE HUMORAL IMMUNITY ACTIVATION CAUSES THE BLADDER OUTLET OBSTRUCTION RELATED WITH PROSTATE THROUGH THE DIFFERENT MECHANISM FROM THE PROSTATE VOLUME

You have accessJournal of UrologyCME1 Apr 2023PD02-10 THE HUMORAL IMMUNITY ACTIVATION CAUSES THE BLADDER OUTLET OBSTRUCTION RELATED WITH PROSTATE THROUGH THE DIFFERENT MECHANISM FROM THE PROSTATE VOLUME Hidenori Akaihata, Yuki Harigane, Kei Yaginuma, Yu Endo, Yuki Yoshida, Hitomi Imai, Yuta Matsuoka, Akifumi Onagi, Kanako Matsuoka, Seiji Hoshi, Tomoyuki Koguchi, Junya Hata, Yuichi Sato, Masao Kataoka, Motohide Uemura, and Yoshiyuki Kojima Hidenori AkaihataHidenori Akaihata More articles by this author , Yuki HariganeYuki Harigane More articles by this author , Kei YaginumaKei Yaginuma More articles by this author , Yu EndoYu Endo More articles by this author , Yuki YoshidaYuki Yoshida More articles by this author , Hitomi ImaiHitomi Imai More articles by this author , Yuta MatsuokaYuta Matsuoka More articles by this author , Akifumi OnagiAkifumi Onagi More articles by this author , Kanako MatsuokaKanako Matsuoka More articles by this author , Seiji HoshiSeiji Hoshi More articles by this author , Tomoyuki KoguchiTomoyuki Koguchi More articles by this author , Junya HataJunya Hata More articles by this author , Yuichi SatoYuichi Sato More articles by this author , Masao KataokaMasao Kataoka More articles by this author , Motohide UemuraMotohide Uemura More articles by this author , and Yoshiyuki KojimaYoshiyuki Kojima More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003219.10AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The prostate volume and morphological features of the prostate are well known to be associated with bladder outlet obstruction (BOO) in the male patients. However, the causative agents and factors of BOO are multifactorial and incompletely understood. This study aims to find out the novel mechanism underlying bladder outlet obstruction (BOO) except for prostate volume and morphological features by comprehensive gene expression analysis (CGEA). METHODS: A total of 31 patients who had a diagnosis of benign by the random prostate biopsy were enrolled in this study. CGEA was performed with prostate specimens obtained by the biopsy. The patients were divided into control group (prostate volume <30 mL) and benign prostatic enlargement (BPE) group (prostate volume ≥30 mL). Hierarchical clustering was performed to identify the clusters with similar gene expression by the genes indicated significantly different between two groups by t-test. The uroflowmetry parameters were compared among each cluster. The protocol was approved by the ethics committee of Fukushima Medical University. RESULTS: CGEA selected 12 genes with significant difference in mean converted value between control and BPE (p<0.01) from 11,907 genes. Hierarchical clustering analysis using these 12 genes categorized three different clusters: the control (n=8), the BPE (n=11) and BPE with inflammatory (n=12) clusters. As compared BPE cluster, the BPE with inflammatory cluster have activation of humoral immunity (increased VSIG2 gene), more suppression of estrogen receptor signaling (reduced ELK4 gene) and more decreased angiogenesis (reduced MME gene). The maximum flow rate was significantly lower in the BPE with inflammatory cluster than in the control cluster (p=0.03). There was no significant difference about the maximum flow rate between control cluster and BPE cluster. CONCLUSIONS: Our results suggested that humoral immunity activation, estrogen receptor signaling suppression and decreased angiogenesis reduced maximal urinary flow rate in the patients with large prostate volume. The activation of humoral immunity in addition to the change of estrogen receptor signaling and angiogenesis causes BOO related with prostate through the different mechanism from the prostate volume. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e72 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Hidenori Akaihata More articles by this author Yuki Harigane More articles by this author Kei Yaginuma More articles by this author Yu Endo More articles by this author Yuki Yoshida More articles by this author Hitomi Imai More articles by this author Yuta Matsuoka More articles by this author Akifumi Onagi More articles by this author Kanako Matsuoka More articles by this author Seiji Hoshi More articles by this author Tomoyuki Koguchi More articles by this author Junya Hata More articles by this author Yuichi Sato More articles by this author Masao Kataoka More articles by this author Motohide Uemura More articles by this author Yoshiyuki Kojima More articles by this author Expand All Advertisement PDF downloadLoading ...

MP20-17 LARD DIET PROMOTES PROSTATE CANCER PROGRESSION THROUGH MODULATING GUT MICROBIOTA AND INTRATUMORAL LIPID METABOLISM

You have accessJournal of UrologyCME1 Apr 2023MP20-17 LARD DIET PROMOTES PROSTATE CANCER PROGRESSION THROUGH MODULATING GUT MICROBIOTA AND INTRATUMORAL LIPID METABOLISM Hiromi Sato, Shintaro Narita, Yoshiko Takahashi, Masanori Ishida, Mizuki Kobayashi, Soki Kasima, Ryohei Yamamoto, Taketoshi Nara, Mingguo Huang, Kazuyuki Numakura, Mitsuru Saito, Toshiaki Yoshioka, and Tomonori Habuchi Hiromi SatoHiromi Sato More articles by this author , Shintaro NaritaShintaro Narita More articles by this author , Yoshiko TakahashiYoshiko Takahashi More articles by this author , Masanori IshidaMasanori Ishida More articles by this author , Mizuki KobayashiMizuki Kobayashi More articles by this author , Soki KasimaSoki Kasima More articles by this author , Ryohei YamamotoRyohei Yamamoto More articles by this author , Taketoshi NaraTaketoshi Nara More articles by this author , Mingguo HuangMingguo Huang More articles by this author , Kazuyuki NumakuraKazuyuki Numakura More articles by this author , Mitsuru SaitoMitsuru Saito More articles by this author , Toshiaki YoshiokaToshiaki Yoshioka More articles by this author , and Tomonori HabuchiTomonori Habuchi More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003245.17AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Lard diet (LD) is a risk factor for prostate cancer (PCa) progression. The role of dietary dysbiosis in the development of PCa is largely unknown, even though it has recently become clear that it plays a significant role in progression of many cancers. Herein, we performed a comprehensive gut microbiome and intratumoral mRNA omics analyses to analyze targetable molecules involved in LD-induced PCa progression via gut microbial alteration. METHODS: Pb-Cre; Pten (fl/fl) transgenic mice and C57BL6 mice subcutaneously inoculated with TRAMP-C2 PCa cells were fed with a LD rich in saturated fatty acid (SFA) or fish- oil diet (FOD) rich in polyunsaturated fatty acid. We obtained fecal and prostate/subcutaneous tumor samples. Using 16S rRNA gene amplicon sequencing, we compared the diversity and relative abundance of gut microbiota. We performed a cDNA microarray to assess the mRNA expression in the mouse PCa tissue. RESULTS: More weight and prostate/subcutaneous tumor volume were gained by the LD-fed mice in two mouse models compared to the FOD-fed mice. In an integrated analysis of the two models, the LD group and the FOD group formed different gut microbial clusters. According to microbiome analysis, order Lactobacillales was relatively more abundant in the FOD group than in the LD group, and order Clostridiales was enriched in the LD group compared to the FOD group. The proportion of order Lactbacillales in the gut was negatively associated with the body weight and prostate weight of the mice. In microarray analysis, we found the modulation of lipid metabolism and cholesterol biosynthesis pathways with 10 significantly modulated genes including sphingosine 1-phosphate receptor 2 (S1PR2) and low-density lipoprotein receptor (LDLR) in PCa tissues. Of these genes, S1PR2 was highly correlated with the abundance of order Lactobacillales in the mouse gut. Moreover, PCa patients with a higher Gleason score (≥8) and a higher body mass (BMI) index had significantly lower S1PR2 RNA levels in human prostatic specimens than those with a Gleason score ≤ 7 and lower BMI. CONCLUSIONS: SFA may accelerate PCa progression by altering particular gut microbial species and lipogenic genes in PCa. Therapeutics with alteration of gut microbiota and candidate genes involved in diet-induced PCa progression may be attractive in PCa. Source of Funding: GlaxoSmithKline plc © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e282 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Hiromi Sato More articles by this author Shintaro Narita More articles by this author Yoshiko Takahashi More articles by this author Masanori Ishida More articles by this author Mizuki Kobayashi More articles by this author Soki Kasima More articles by this author Ryohei Yamamoto More articles by this author Taketoshi Nara More articles by this author Mingguo Huang More articles by this author Kazuyuki Numakura More articles by this author Mitsuru Saito More articles by this author Toshiaki Yoshioka More articles by this author Tomonori Habuchi More articles by this author Expand All Advertisement PDF downloadLoading ...

Robotically controlled three-dimensional micro-ultrasound for prostate biopsy guidance.

Prostate imaging to guide biopsy remains unsatisfactory, with current solutions suffering from high complexity and poor accuracy and reliability. One novel entrant into this field is micro-ultrasound (microUS), which uses a high-frequency imaging probe to achieve very high spatial resolution, and achieves prostate cancer detection rates equivalent to multiparametric magnetic resonance imaging (mpMRI). However, the ExactVu transrectal microUS probe has a unique geometry that makes it challenging to acquire controlled, repeatable three-dimensional (3D) transrectal ultrasound (TRUS) volumes. We describe the design, fabrication, and validation of a 3D acquisition system that allows for the accurate use of the ExactVu microUS device for volumetric prostate imaging. The design uses a motorized, computer-controlled brachytherapy stepper to rotate the ExactVu transducer about its axis. We perform geometric validation using a phantom with known dimensions and compare performance with magnetic resonance imaging (MRI) using a commercial quality assurance anthropomorphic prostate phantom. Our geometric validation shows accuracy of 1mm or less in all three directions, and images of an anthropomorphic phantom qualitatively match those acquired using MRI and show good agreement quantitatively. We describe the first system to acquire robotically controlled 3D microUS images using the ExactVu microUS system. The reconstructed 3D microUS images are accurate, which will allow for future applications of the ExactVu microUS system in prostate specimen and in vivo imaging.

A matched case-control study in Taiwan to evaluate potential risk factors for prostate cancer

The rising incidence rate of prostate cancer (PCa) worldwide has become a public health concern. PCa has a multifactorial etiology, and the link between human papillomavirus (HPV) and PCa has been widely investigated by numerous case–control studies. This age-matched, case–control study included 143 PCa patients and 135 benign prostatic hyperplasia (BPH) patients, with prostatic specimens testing negative for malignancy, as control. Study participants were recruited from four major hospitals in Taoyuan City, Taiwan, period 2018–2020, looking into HPV infection and other PCa risk factors, including dietary habits, family history, personal lifestyle, and sexual behavior. Multiple logistic regression analysis and forward stepwise selection analysis were conducted to identify potential risk factors for PCa. HPV DNA was found in 10 of the 143 PCa cases (7%) and 2 of the 135 BPH controls (1.5%) (OR = 6.02, 95% CI = 1.03–30.3, p = 0.046). This association was slightly significant, and furthermore, high risk HPV was not found to be associated with PCa. Higher body mass index (BMI) (OR = 1.15, 95% CI = 1.05–1.27, p = 0.003), more total meat consumption (OR = 2.74, 95% CI = 1.26–5.94, p = 0.011), exhibited association to PCa. However, PCa family history only presented a statistically significant difference by forward stepwise analysis (OR = 3.91, 95% CI = 1.17–13.12, p = 0.027). While much focus has been on the association between HPV and PCa, the results of this study indicate that more efforts should be directed towards investigating dietary habits, personal lifestyle and family history as factors for PCa. These results could serve as a basis for designing PCa prevention strategies.

Is transrectal ultrasound or magnetic resonance imaging better at estimating prostatic volume for patients with prostate cancer?

314 Background: Determining the correct size (volume) of the prostate is imperative for patients with prostate cancer. Prostate size can affect many parameters in patient care such as cores in a biopsy taken and available treatment options. Traditionally, most patients underwent transrectal ultrasound (TRUS) during prostate biopsy to estimate prostatic volume. While TRUS is still used to estimate prostate volume, more recently prostate Magnetic Resonance Imaging (MRI) has also come into favor. Current literature indicates MRI is more accurate than TRUS for prostate size, but few studies exist, and whether differences in the two are clinically significant remains uncertain. The purpose of this study was to compare prostate volumes from TRUS and MRI to gross specimens after prostatectomy. Methods: Patients who underwent radical prostatectomy for prostate cancer between 2017–2022 were identified. TRUS and MRI measurements closest to the date of surgery were obtained. These were compared to gross prostate specimens after surgery, which was considered the gold standard. All TRUS volumes were recorded by a urologist during prostate biopsy using the ellipsoid formula (L*W*H*(π/6)). MRI measurements were done by a radiologist also using the ellipsoid formula. The weight and dimensions of gross specimens were measured by a pathologist. Ellipsoid formula was then used to calculate final volume measurements in gross specimens. Paired samples t-test was used to compare averages of TRUS and MRI to the gross specimen. Results: 83 patients were included in the study with an average age at prostatectomy of 65.47 years. TRUS volume significantly differed from gross specimen volume by an average of –4.56 mL (p=0.017) and gross specimen weight by -14.31 g (p &lt;0.001). MRI volume was not significantly different from gross specimen volume, by an average of –0.56 mL (p=0.771) and was significantly different from prostate weight by –10.32 g (p &lt;0.001). When compared to one another, TRUS and MRI significantly differed on average by –4 mL (p=0.033). Conclusions: MRI is more accurate than TRUS to estimate prostate volume. Both MRI and TRUS underestimate prostate weight. Urologists should be aware of potential inaccuracies when assessing preoperative prostate volume with TRUS, and recognize MRI is the best predictor of size. While imperfect, TRUS is still relatively accurate measuring prostate volume, and given its ease of availability and cost, we feel it is a useful modality to determine prostate size. [Table: see text]

Evaluation of TURP specimen with special reference to prostatic intraepithelial neoplasia and prostatic cancer using light microscopy and immunohistochemical markers of P63, CK5/6, AMACR (p504s), and PSA

Background: Prostate cancer is the world’s leading cause of cancer and the second cause of cancer-related death in men after lung cancer. The incidence of prostatic carcinoma is increasing with age. Prostate intraepithelial neoplasia can only be diagnosed by histopathological examination of prostate tissue. In practice, small foci of cancer and several morphological mimickers of different Gleason Grades were encountered leading to diagnosing difficulty. To overcome this pitfall, the use of HMW Cytokeratin’s 5 and 6 (CK5/6) or p63 or combination of these two with alpha-methyl acyl- COA-racemase (AMACR) is triple cocktail which is recommended. Aims and Objectives: The objectives of this study were to analyze the histomorphology of various non-neoplastic and neoplastic lesions of the prostate and to know the incidence of prostatic intraepithelial neoplasia in transurethral resection of prostate (TURP) specimen, to assess the usefulness of immunohistochemical analysis with a panel of markers (p63, CK5/6, AMACR [p504s], and prostate-specific antigen [PSA]) to confirm the diagnosis of prostatic intraepithelial neoplasia and prostate cancer, and to differentiate several benign mimickers of prostatic adenocarcinoma. Materials and Methods: It is a prospective study performed for 18 month from January 2020 to June 2021. Thirty TURP specimens were collected in 10% formalin and processed in the department of pathology, MCH, Kolkata. Results: In the present study, benign prostatic hyperplasia formed majority of cases (80%). The presence of AMACR and absence of basal cell specific marker p63 and CK5/6 confirm the presence of prostate cancer. Conclusion: High degree of association of HGPIN with prostatic Carcinoma, it is suggested that these HGPIN patients need close follow-up, observation, and investigation to rule out existence of carcinoma, especially in the peripheral zone.

Utility of p63 and Alpha Methyl Acyl CoA Racemase in the Lesions of Prostatic Mimickers: An Observational Study

Introduction: Prostate adenocarcinoma is the most commonly occurring cancer in men. Differentiation of prostatic adenocarcinoma from prostatic mimickers sometimes difficult on the sole basis of histologic findings. Diagnosis of carcinoma is based on Immunohistochemistry (IHC) by negative immune reaction with p63 and positive staining with Alpha Methyl Acyl CoA Racemase (AMACR). Aim: To evaluate the utility of p63 and AMACR in the prostatic mimickers. Materials and Methods: In this analytical observational study, all prospective prostatic mimickers with transrectal ultrasound (TRUS) guided biopsies received in the pathology department of Bharati Vidyapeeth Medical College, Pune, India in a tertiary care hospital from July 2020 to July 2022 were studied. 70 cases were collected, studied and analysed which included 38 Transurethral Resection of the Prostate (TURP) specimens and 32 TRUS guided tissue biopsies. The Haematoxylin &amp; Eosin (H&amp;E) stained slides of all the cases were examined and divided into three categories-malignant (08 cases), prostatic mimickers (53 cases) and suspicious for malignancy (09 cases). Furthur, these cases were subjected to IHC for p63 and AMACR. Statistical Package for Social Sciences (SPSS) version 25.0 software was used for data analysis using chi square test along with p-value. Results: Out of the 53 cases of prostatic mimickers and 09 cases were suspicious for malignancy, 56 were positive for p63 and 06 were negative for p63. There was a statistically significant association between p63 IHC staining and the differentiation of benign cases from malignant prostatic lesions (p&lt;0.001). The sensitivity and specificity of p63 were 93.3% and 100% respectively. There were 08 cases of prostate adenocarcinoma stained with AMACR, all were positive. The sensitivity and specificity being 100%. Results revealed that there was a significant statistical association between the positive IHC staining of AMACR and prostatic adenocarcinoma (p&lt;0.001). Conclusion: The diagnostic performance of p63 and AMACR proves to be significant in differentiating between the mimickers of prostatic lesions and adenocarcinoma. IHC is recommended to reduce diagnostic error in suspected cases.

Histopathological Findings in Prostatic Chips and its Correlation with Prostate Specific Antigen Levels

Objectives: To determine the pattern of histological findings in prostatic chips obtained from cases of enlarged prostate gland and to correlate the findings with PSA levels. Materials and Methods: It was a cross sectional descriptive study conducted in Northwest General Hospital , Peshawar from 1st January 2018 to 23rd December 2021. A total of 500 male cases with features of enlarged prostate, frequency, urgency and dribbling with mean age of 52 ± 12.3 years (range 45 -80 years) were included in the study. The prostatic biopsy specimens were obtained and PSA levels were done in all cases. The histological specimens were subjected to microscopic examinations and findings were recorded in proforma. The findings were correlated with the PSA levels. Mean and standard deviation were used for quantitative data. Frequency and percentages were used for qualitative data Results: Out of 500 cases of enlarged prostate, benign prostate hypertrophy was seen in 375 (75%) cases. 125 cases (25%) had micro invasive carcinoma prostate . All 375 cases of benign prostate hypertrophy had prostate specific antigen levels less than 4ng. Out of 125 cases of micro invasive carcinoma, 120 (96%) had PSA levels &gt;10ng . Sensitivity of PSA at levels of 10ng/ml for prostatic carcinoma was 96%. Conclusion: Benign prostate hypertrophy is the commonest lesion in cases of prostate pathology. PSA is useful marker to determine the presence or absence of micro invasive carcinoma in patients with prostate hypertrophy. Keywords: Benign prostate hypertrophy, micro invasive carcinoma prostate, prostate specific antigen.

Analysis of aberrant miRNA-mRNA interaction networks in prostate cancer to conjecture its molecular mechanisms.

MicroRNAs (miRNAs) capable of post-transcriptionally regulating mRNA expression are essential to tumor occurrence and progression. This study aims to find negatively regulatory miRNA-mRNA pairs in prostate adenocarcinoma (PRAD). Combining The Cancer Genome Atlas (TCGA) RNA-Seq data with Gene Expression Omnibus (GEO) mRNA/miRNA expression profiles, differently expressed miRNA/mRNA (DE-miRNAs/DE-mRNAs) were identified. MiRNA-mRNA pairs were screened by miRTarBase and TarBase, databases collecting experimentally confirmed miRNA-mRNA pairs, and verified in 30 paired prostate specimens by real-time reverse transcription polymerase chain reaction (RT-qPCR). The diagnostic values of miRNA-mRNA pairs were measured by receiver operation characteristic (ROC) curve and Decision Curve Analysis (DCA). DAVID-mirPath database and Connectivity Map were employed in GO/KEGG analysis and compounds research. Interactions between miRNA-mRNA pairs and phenotypic features were analyzed with correlation heatmap in hiplot. Based on TCGA RNA-Seq data, 22 miRNA and 14 mRNA GEO datasets, 67 (20 down and 47 up) miRNAs and 351 (139 up and 212 down) mRNAs were selected. After screening from 2 databases, 8 miRNA (up)-mRNA (down) and 7 miRNA (down)-mRNA (up) pairs were identified with Pearson's correlation in TCGA. By external validation, miR-221-3p (down)/GALNT3 (up) and miR-20a-5p (up)/FRMD6 (down) were chosen. The model combing 4 signatures possessed better diagnostic value. These two miRNA-mRNA pairs were significantly connected with immune cells fraction and tumor immune microenvironment. The diagnostic model containing 2 negatively regulatory miRNA-mRNA pairs was established to distinguish PRADs from normal controls.

18F-PSMA Cerenkov Luminescence and Flexible Autoradiography Imaging in a Prostate Cancer Mouse Model and First Results of a Radical Prostatectomy Feasibility Study in Men.

Intraoperative identification of positive resection margins (PRMs) in high-risk prostate cancer (PC) needs improvement. Cerenkov luminescence imaging (CLI) with 68Ga-PSMA-11 is promising, although limited by low residual activity and artificial signals. Here, we aimed to assess the value of CLI and flexible autoradiography (FAR) with 18F-PSMA-1007. Methods: Mice bearing subcutaneous PSMA-avid RM1-PGLS tumors were administered 18F-PSMA-1007, and PET/CT was performed. After the animals had been killed, organs were excised and measured signals in CLI and FAR CLI were correlated with tracer activity concentrations (ACs) obtained from PET/CT. For clinical assessment, 7 high-risk PC patients underwent radical prostatectomy immediately after preoperative 18F-PSMA PET/CT. Contrast-to-noise ratios (CNRs) were calculated for both imaging modalities in intact specimens and after incision above the index lesion. Results: In the heterotopic invivo mouse model (n = 5), CLI did not detect any lesion. FAR CLI detected a distinct signal in all mice, with a lowest AC of 7.25 kBq/mL (CNR, 5.48). After incision above the index lesion of the prostate specimen, no increased signal was observed at the cancer area in CLI. In contrast, using FAR CLI, a signal was detectable in 6 of 7 patients. The AC in the missed index lesion was 1.85 kBq/mL, resulting in a detection limit of at least 2.06 kBq/mL. Histopathology demonstrated 2 PRMs, neither of which was predicted by CLI or FAR CLI. Conclusion: 18F-PSMA FAR CLI was superior to CLI in tracer-related signal detectability. PC was could be visualized in radical prostatectomy down to 2.06 kBq/mL. However, the detection of PRMs was limited. Direct anatomic correlation of FAR CLI is challenging because of the scintillator overlay.

Incidence of prostatic intraepithelial neoplasia in TURP specimens with special reference to p63 expression in various lesions of prostate

Introduction: Prostate cancer is the second common malignancy in men. Prostatic intraepithelial neoplasia (PIN) is the precursor lesion of prostatic carcinoma. Histopathological examination is necessary to diagnose PIN lesions. Objective: The aim of the study is to determine the incidence of Prostatic intraepithelial neoplasia and to analyse the usefulness of basal cell marker p63 expression in various lesions of prostate. Methods: This is a two-year prospective study of 65 transurethral resection specimens of prostate, carried out in the Department of pathology, Dr B R Ambedkar Medical College, Bangalore. mmunohistochemical marker p63 is used and its expression in various lesions was analysed. Results: Out of 65 cases studied, 4 were inflammatory lesions, 52 were benign prostatic hyperplasia (BPH) and 9 were malignant lesions. Low grade PIN was identified in 8(12.3%) cases of BPH. High grade PIN was seen in 9(13.8%) cases and tufting pattern was the commonest. HGPIN was predominantly associated with adenocarcinoma. p63 was expressed in all the benign glands in BPH and HGPIN. Malignant glands were negative for p63 expression.

Protective Effects of PollenAid Plus Soft Gel Capsules' Hydroalcoholic Extract in Isolated Prostates and Ovaries Exposed to Lipopolysaccharide.

Pollen extract represents an innovative approach for the management of the clinical symptoms related to prostatitis and pelvic inflammatory disease (PID). In this context, the aims of the present work were to analyze the phenolic composition of a hydroalcoholic extract of PollenAid Plus soft gel capsules, and to evaluate the extract’s cytotoxic effects, in human prostate cancer PC3 cells and human ovary cancer OVCAR-3 cells. Additionally, protective effects were investigated in isolated prostate and ovary specimens exposed to lipopolysaccharide (LPS). The phytochemical investigation identified catechin, chlorogenic acid, gentisic acid, and 3-hydroxytyrosol as the prominent phenolics. The extract did not exert a relevant cytotoxic effect on PC3 and OVCAR-3 cells. However, the extract showed a dose-dependent inhibition of pro-inflammatory IL-6 and TNF-α gene expression in prostate and ovary specimens, and the extract was effective in preventing the LPS-induced upregulation of CAT and SOD gene expression, which are deeply involved in tissue antioxidant defense systems. Finally, a docking approach suggested the capability of catechin and chlorogenic acid to interact with the TRPV1 receptor, playing a master role in prostate inflammation. Overall, the present findings demonstrated anti-inflammatory and antioxidant effects of this formulation; thus, suggesting its capability in the management of the clinical symptoms related to prostatitis and PID.

Digital real-time microscopy of ex-vivo tissues: A novel strategy to control surgical accuracy.

Ex-vivo FCM is a novel digital optical technique that provides images of fresh tissues in a real-time fashion with magnification to subcellular details of a flattened unprocessed sample. Digital images are hematoxylin-eosin-like and can be shared and interpreted remotely. In urology, FCM has been successfully applied for prostate tissue interpretation, either during biopsy and radical prostatectomy. Possible applications of FCM may reflect those of frozen section analysis and can be extended to all fields in which the intra-operative microscopical control is advisable. This is an investigative prospective case series that aims to explore FCM feasibility in novel surgical settings and provide a depiction of FCM digital images in those fields. The definite purpose is to check the accuracy of surgical specimen during the following interventions: (a) trans-urethral resection of bladder tumors, to confirm the presence of muscular layer; (b) biopsy of a retroperitoneal mass, to check for the location and quality of cores; (c) training in robotic radical prostatectomy, to control surgical margins after a nerve sparing performed by a trainee. To this aim, we collected FCM images during seven surgical procedures. FCM findings were compared to those from the final histopathological analysis and the agreement was assessed. In all cases, FCM digital images were obtained in the OR. FCM was able to confirm the presence of muscular layer in TURB specimen, the presence of lymphomatous tissue, surgical margins at prostate specimen. FCM intra-operative interpretation was consistent with final histopathology in all cases. Ex vivo FCM may represent a novel approach to control the quality of specimens, likely to tailor surgical strategy in a real-time fashion. Moreover, digitalization represents a step toward the implementation of telepathology in clinical practice.

Poster 11 - A 10 Year Retrospective Analysis of Transurethral Resection of Prostate specimens at an Irish Academic Centre 2012–2021

Poster 11 - A 10 Year Retrospective Analysis of Transurethral Resection of Prostate specimens at an Irish Academic Centre 2012–2021

Multiparametric MRI for Staging of Prostate Cancer: A Multicentric Analysis of Predictive Factors to Improve Identification of Extracapsular Extension before Radical Prostatectomy.

Simple SummaryIn this multicentric study, we tested the accuracy of multiparametric magnetic resonance imaging (mpMRI) in detecting extracapsular extension (ECE) out of the prostate in order to plan surgical sparing of neurovascular bundles in radical prostatectomy. Univariate and multivariate logistic regression analyses were performed to identify other risk factors for ECE. We found that it has a good ability to exclude extracapsular extension but a poor ability to identify it correctly. Risk factors other than mpMRI that predicted ECE were as follows: prostatic specific antigen, digital rectal examination, ratio of positive cores, and biopsy grade group. We suggest that using mpMRI exclusively should not be recommended to decide on surgical approaches.The correct identification of extracapsular extension (ECE) of prostate cancer (PCa) on multiparametric magnetic resonance imaging (mpMRI) is crucial for surgeons in order to plan the nerve-sparing approach in radical prostatectomy. Nerve-sparing strategies allow for better outcomes in preserving erectile function and urinary continence, notwithstanding this can be penalized with worse oncologic results. The aim of this study was to assess the ability of preoperative mpMRI to predict ECE in the final prostatic specimen (PS) and identify other possible preoperative predictive factors of ECE as a secondary end-point. We investigated a database of two high-volume hospitals to identify men who underwent a prostate biopsy with a pre-biopsy mpMRI and a subsequent RP. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of mpMRI in predicting ECE were calculated. A univariate analysis was performed to find the association between image staging and pathological staging. A multivariate logistic regression was performed to investigate other preoperative predictive factors. A total of 1147 patients were selected, and 203 out of the 1147 (17.7%) patients were classified as ECE according to the mpMRI. ECE was reported by pathologists in 279 out of the 1147 PS (24.3%). The PPV was 0.58, the NPV was 0.72, the sensitivity was 0.32, and the specificity was 0.88. The multivariate analysis found that PSA (OR 1.057, C.I. 95%, 1.016–1.100, p = 0.006), digital rectal examination (OR 0.567, C.I. 95%, 0.417–0.770, p = 0.0001), ratio of positive cores (OR 9.687, C.I. 95%, 3.744–25.006, p = 0.0001), and biopsy grade in prostate biopsy (OR 1.394, C.I. 95%, 1.025–1.612, p = 0.0001) were independent factors of ECE. The mpMRI has a great ability to exclude ECE, notwithstanding that low sensitivity is still an important limitation of the technique.

PD-L1 positive lympho-epithelial lesions in inflammatory prostate.

Ductal epithelial changes (lympho-epithelial lesions-LEL) in prostatic chronic inflammation (CI) are not well studied so far. to investigate LEL immediately adjacent to prostatic CI. We studied LEL in 144 prostatic surgical and autopsy specimens in various types of prostatic CI: NIH-category IV prostatitis (histologic prostatitis-HP), nonspecific granulomatous prostatitis (NSGP), and the reactive lymphoid infiltrates in the vicinity of benign prostatic hyperplasia (BPH) and prostate adenocarcinoma (PCa). CI is scored as low and high grade (LG, HG) according to the severity of inflammation. LEL was identified in all types of prostatic specimens and in all types of prostatic CI: in 70.9% of patients with HP; in 100% of cases with NSGP; in 68.7% and in 80% adjacent to BPH and PCa respectively. Statistical analysis showed a significant correlation of the presence of LEL with HG CI (p<0.001). LEL showed strong membranous PD-L1 expression. The study presents the first attempt to examine LEL in inflammatory human prostate. PD-L1 positive LEL have no diagnostic organ specificity, although they are a constant histological finding in HG prostatic CI. LEL, inducible after birth by CI, are an integral part of prostate-associated lymphoid tissue (PALT) and of the inflammatory prostatic microenvironment.