Diagnosis Of Prostatic Adenocarcinoma Research Articles

Abstract PO2-20-05: Onco-Genome Brazil: Mapping Breast and Prostate Cancer in the Brazilian Public Health System

Abstract Background: Breast and prostate cancers are the most common malignancies diagnosed in women and men respectively, and present with great clinical heterogeneity, even in tumors with the same phenotypic characteristics. Somatic and germline molecular alterations in DNA may have prognostic and predictive impact, influencing response to therapies and overall survival. In addition, the evaluation of germline mutations can help identify individuals and families at higher risk for developing cancer. Aims: Our aim is to characterize the somatic and germline genomic landscape of women with locally advanced HER2-positive breast cancer and men with metastatic prostate cancer from Brazil. Secondarily, we aim to identify genetic variants associated with tumor prognosis and treatment response, identify patients carrying pathogenic alterations in cancer-predisposing genes, and characterize the genetic ancestry of the population included in the study. Trial design: This observational multicenter cohort study (NCT05306600) will include 550 adult patients from the five macro-regions of Brazil, divided into two arms: 1) breast cancer and 2) prostate cancer. Clinical and pathological data will be collected, as well as DNA samples from peripheral blood and tumor tissue. Whole-exome sequencing (WES) will be performed to identify variants that may be drivers and/or actionable in a specific patient or tumor. These variants will be interpreted and classified according to their population frequencies, in silico predictors, functional studies, and literature data, following international guidelines proposed by expert societies. This trial is supported by the Ministry of Health in Brazil and includes patients of the Public Health System. Eligibility criteria: In arm 1, the inclusion criteria are patients with a histological diagnosis of breast carcinoma with overexpression of HER-2, clinical stage II or III, and undergoing neoadjuvant treatment with chemotherapy plus trastuzumab. In arm 2, the criteria are patient with histological diagnosis of prostate adenocarcinoma, currently in clinical stage IV. Patients without availability of biological material collection are excluded from the study, as well as patients in whom there was no central confirmation of required histology. Statistical methods: Univariate and multivariate analyses will be conducted to evaluate the possible effect of specific genes or mutations on the investigated outcomes, including tumor prognosis and treatment response. Discussion: Currently, 265 participants have already been included in the study, 150 in arm 1 and 115 in arm 2. This trial will contribute to the construction of a robust database that should provide a better understanding of the genomic profile of patients with breast and prostate cancer in Brazil. For more information about the trial, please contact Daniela Rosa (daniela.rosa@hmv.org.br). Citation Format: Jaqueline Schuch, Cláudia Bordignon, Mahira Rosa, Angélica de Baumont, Marina Bessel, Gabriel Macedo, Daniela Rosa. Onco-Genome Brazil: Mapping Breast and Prostate Cancer in the Brazilian Public Health System [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-20-05.

Mapping breast and prostate cancer in the Brazilian public health system: study protocol of the Onco-Genomas Brasil.

Breast and prostate cancers are the most common malignancies diagnosed in women and men respectively, and present with great clinical heterogeneity, even in tumors with the same histology and same site of origin. Somatic and germline molecular alterations in DNA may have prognostic and predictive impact, influencing response to therapies and overall survival. Our aim is to characterize the somatic and germline genomic landscape of women with locally advanced HER2-positive breast cancer and men with metastatic prostate cancer in Brazil. Secondarily, we aim to identify genetic variants associated with tumor prognosis and treatment response, identify patients carrying pathogenic alterations in cancer-predisposing genes, and characterize the genetic ancestry of the population included in the study. This observational multicenter cohort study will include 550 adult patients from the five macro-regions of Brazil, divided into two arms: 1) breast cancer and 2) prostate cancer. Clinical and pathological data will be collected, as well as DNA samples from peripheral blood and tumor samples. In arm 1, the inclusion criteria are a histological diagnosis of breast carcinoma with overexpression of HER-2, clinical stage II or III, and current neoadjuvant treatment with chemotherapy plus trastuzumab. In arm 2, the criterion is a histological diagnosis of prostate adenocarcinoma, clinical stage IV. Whole-exome sequencing (WES) will be performed to identify variants that may be drivers and/or actionable in a specific patient or tumor. These variants will be interpreted and classified according to their population frequencies, in silico predictors, functional studies, and literature data, following international guidelines proposed by expert societies. This trial will contribute to the construction of a robust database that should provide a better understanding of the genomic profile of patients with breast and prostate cancer in Brazil. Considering the miscegenation of the Brazilian population, knowledge generated from these data will have implications for future studies of this specific population. [clinicaltrial.gov], identifier [NCT05306600].

Exploring the Relationship between E-Cadherin and β-Catenin Cell Adhesion Proteins and Periacinar Retraction Clefting in Prostatic Adenocarcinoma.

Periacinar retraction clefts represent a histopathological criterion supporting the diagnosis of prostatic adenocarcinoma. The origin of these clefts in prostatic adenocarcinoma remains unclear. Exploring the established functions of E-cadherin and β-catenin as intercellular adhesion proteins, and aiming to elucidate the origin of periacinar retraction clefting, we conducted a correlation study between the immunohistochemical expression of E-cadherin and β-catenin and the presence of periacinar retraction clefts in prostatic adenocarcinoma. We examined 53 cases of morphologically diagnosed prostatic adenocarcinoma, assessing both the neoplastic and adjacent nonneoplastic prostatic tissues for the existence and degree of periacinar retraction clefts. Additionally, we analyzed the immunohistochemical expression of E-cadherin and β-catenin proteins in prostatic tissue and explored their correlation with periacinar retraction clefts, and Gleason score, Grade Group, preoperative serum prostate specific-antigen (sPSA) levels, surgical margin status, and Tumor, Node, Metastasis (TNM) stage in prostatic adenocarcinoma. Our study confirms that periacinar retraction clefting is significantly more extensive in prostatic adenocarcinoma than in nonneoplastic prostatic tissue (p < 0.001). We report a decreased expression of E-cadherin and β-catenin immunostaining in prostatic adenocarcinoma and a negative correlation with Gleason score and Grade Group. Periacinar retraction clefting positively correlated with E-cadherin and β-catenin ((rho = 0.350; p = 0.010) and (rho = 0.340; p = 0.012)) immunostaining in prostatic adenocarcinoma. Periacinar retraction clefts stand out as a dependable criterion in the diagnosis of prostatic adenocarcinoma. E-cadherin and β-catenin proteins are potential markers indicative of tumor progression and invasiveness in prostatic adenocarcinoma. Our discovery of a positive correlation between immunostaining of E-cadherin and β-catenin proteins and periacinar retraction clefts in prostatic adenocarcinoma aligns with the notion that periacinar retraction clefting is more characteristic of Gleason Grade3 pattern in prostatic adenocarcinomas, whereas the immunohistochemical expression of E-cadherin and β-catenin shows a decrease with increasing histopathological tumor grade.

Role of Alcian Blue Stain in Differentiating Prostatic Adenocarcinoma from Nodular Hyperplasia of Prostate

Objective: Enlargement of prostate is one of the leading cause of morbidity in men. Alcian Blue stain demonstrates that the acidic mucin is present in prostatic adenocarcinoma but absent in nodular hyperplasia of prostste. So this histochemical marker can be used in distinguishing them. This study aims to determine the role of Alcian Blue stain in differentiating prostatic adenocarcinoma from the nodular hyperplasia of prostate. Materials and Methods: This cross-sectional study was conducted in the Department of Pathology, Rajshahi Medical College, Rajshahi and in the Department of Pathology, Bangabandhu Sheikh Mujib Medical University (BSMMU) during the period of March 2018 to February 2020. Specimens were processed routinely for Haematoxilin and Eosin stain. The Alcian Blue stain was performed to demonstrate the presence of acidic mucin and the findings were categorized as positive or negative staining. Statistical analyses was carried out by using the Statistical package for Social Sciences (SPSS) version 20 for Windows. The components of accuracy test were computed by respective formulae for the tests. Result: The study involved a total 60 specimens of prostatic tissue among which 30 were histopathologically diagnosed cases of prostatic adenocarcinoma and another 30 were histopathologically diagnosed cases of nodular hyperplasia. Among the 30 cases of prostatic adenocarcinoma the acidic mucin was positive in 25 (83.3 %) cases and negative in 5 (16.7%) cases but in nodular hyperplasia it was positive in 8 (26.6%) cases and negative in 22 (73.4%) cases. The sensitivity of Alcian Blue stain in favour of malignancy was 83.3% and specificity was 73.3%. The overall diagnostic accuracy of Alcian Blue stain was 78.3% and it showed a statistically significant difference in staining between the cases of adenocarcinoma and nodular hyperplasia, indicated by p&lt;0.05. Conclusion: Alcian Blue stain has a valuable role in differentiating prostatic adenocarcinoma from the nodular hyperplasia. So it can be used in the diagnosis of prostatic adenocarcinoma. TAJ 2023; 36: No-2: 57-63

Retrospectif Analysing of Anesthesia Manegement in Robotic Assisted Radical Prostatectomy Cases

Aim: In our study, we aimed to investigate anesthesia management, hemodynamic changes and complications that may ocur due to steep trendelenburg, pneumoperitoneum and sugery in RARP patients operated in A.U.T.F, and to evaluate our initial results.&#x0D; Methods: Patients who underwent RARP operation with the diagnosis of prostate adenocarcinoma by the Urology Clinic at Akdeniz University Faculty of Medicine between January 2015 and February 2018 were evaluated retrospectively. Patient’s demographic data, intraoperative hemodynamic and respiratory data, postoperative transfer sites, extubation times, post-extubation blood gas values, complications and discharge times were recorded. Obtained data were analyzed with IBM SPSS® 23.0 program.&#x0D; Results: We found that mean age of the 131 patients included study was 62 years, and mean BMI was 27,6 kg/m2. Also we found that 47 of patients were ASA-I, 69 of patients were ASA-II and 15 of patients were ASA-III. After general evaluation, it was seen that HR, SBP, DBP and MAP decreased significantly in intraoperative period in all patients. There was also a significant decrease in pH and increase in pCO2 in patients due to pneumoperitoneum. In our study, we found thah the most common postoperative complication was nause and vomiting, and the second common was anastomotic leakage. However, none of our patients had a permanent complication. &#x0D; Conclusion: In order to manage anesthesia in RARP, it is necessary to know the physiologic effects of trendelenburg position and pneumoperitoneum on the systems and physiological changes in old age.

Outcomes in Locally Advanced Non-Metastatic Prostate Cancer Presenting with Low PSA at Diagnosis.

Men with low serum prostate-specific antigen (PSA) and high Gleason grade group (GGG) are thought to have poor outcomes compared to high PSA secretors. However, there is limited outcome data to support this. We report clinical outcomes from a single-institutional cohort of men presenting with locally advanced prostate cancer but low serum PSA. Data from electronic database of a UK tertiary cancer center was acquired for men with histological diagnosis of prostate adenocarcinoma, GGG 4 or 5, stage ≥cT3a, and PSA <10ug/L at diagnosis. Men with metastatic disease, or prior androgen deprivation therapy (ADT) were excluded. Biochemical progression was defined as per Phoenix criteria (PSA > nadir+2) for primary radiotherapy, or PSA >0.2 ug/L after primary prostatectomy (and post-operative radiotherapy, if received). Overall survival (OS, from date of diagnosis to death), metastasis-free survival (MFS, from diagnosis to first recorded metastasis or death), and biochemical progression free survival (bPFS, from diagnosis to biochemical progression or death) were estimated by Kaplan Meier method, and multivariable analysis performed using Cox proportional hazards method. Medical records of 7,200 men presenting with non-metastatic prostate cancer from 2013 to 2021 were screened, of which 270 men satisfying the eligibility criteria were included for this study. Initial analysis of 123 men shows median PSA at presentation 7.1 ug/L (IQR 5.6-8.5), and median age 70 years (IQR 65-75). Histology was GGG 4 in 47.6% and 5 in 52.4%. Tumor stage was cT3a in 56.6%, cT3b in 36.9%, and T4 in 6.6%. Pelvic nodes were involved in 5% patients. Majority (83.7%) were treated with radical radiotherapy (external beam alone 64.2%, brachytherapy boost 19.5%), with 24 months ADT; 11.4% underwent radical prostatectomy, and 4.9% received ADT alone. Three men (2.4%) received docetaxel, and one received abiraterone. At a median follow up of 66 months (IQR 27-77), 36 (29.3%) patients had biochemical failure. Total 23 (18.6%) patients had metastases at recurrence, which were visceral in 4%, bone-only in 10%, and nodal-only in 4%. Total 38 (30.6%) patients had died, 23% with prostate cancer and 11% due to other causes. Five-year bPFS was 65.9%, MFS 69.0%, and OS was 77.4%. GGG 5 (versus 4) was associated with significantly worse 5-year bPFS (59.4% vs 73.9%, HR 1.8, 95% CI 1.0-3.2, p = 0.05) and MFS (59.2% vs 81.6%, HR 2.2, 1.2-4.2, p = 0.02). On multivariable analysis including age and PSA at diagnosis, only GGG 5 was associated with worse bPFS (HR 1.8, 1.0-3.3, p = 0.05) and MFS (HR 2.42, 1.25-4.67, p = 0.009). Men with low secreting but high Gleason grade group prostate cancer are a relatively rare group with poor clinical outcomes despite being non-metastatic. Ongoing work (expected completion June 2023) will analyze remaining cases, and compare outcomes within an expanded multicentric cohort with matched controls having elevated PSA at presentation.

The potential role of osteoporosis in unspecific [18F]PSMA-1007 bone uptake.

Unspecific bone uptake is one of the main limitations of PET imaging with some PSMA-targeting radiopharmaceuticals, especially with [18F]PSMA-1007. We explored the potential association between osteoporosis and the occurrence of unspecific [18F]PSMA-1007 bone uptake investigating markers which might correlate with bone mineral density. We retrospectively analyzed treatment-naïve patients with a confirmed diagnosis of prostate adenocarcinoma who underwent staging [18F]PSMA-1007 positron emission tomography (PET). Qualitative image analysis was performed independently by three experienced nuclear medicine physicians. Patients were divided in two groups according to the presence/absence of unspecific bone uptake. Clinical information, blood count parameters (assessed within 3months to the PET scan), body mass index (BMI), and bone density as estimated by computed tomography were collected. The Kruskal-Wallis and t-test were used to compare parameters. We analyzed 77 patients: 29 of them (38%) had unspecific bone uptake at [18F]PSMA-1007 PET, most commonly in the pelvic bones (69%) and ribs (62%). We did not find any significant difference in clinical parameters in the two groups. In patients with unspecific bone uptake, white blood cell, and neutrophil counts were significantly higher; in the same group, we observed lower values of BMI and bone density, although not statistically different. We observed unspecific bone uptake on [18F]PSMA-1007 PET in more than 1/3 of patients. In this exploratory analysis, we found a significant correlation between blood count parameters and unspecific [18F]PSMA-1007 bone uptake. We may speculate that [18F]PSMA-1007 unspecific bone uptake could be associated with osteoporosis. This hypothesis needs to be further investigated in larger populations and exploring more specific markers of osteoporosis.

Finding the Way Back Home: Report of 2 Cases of Oral Metastasis

Around 1-1.5 % of all malignant tumors in oral cavity are caused by metastatic dissemination to this region. Lung, kidney, breast, bone and colorectal regions are primary sites which act as source of metastases to oral cavity. Similarly, metastasis from primary oral malignancy to distant sites is not uncommon with metastasis mainly occurring to lung, followed by bone and liver. Here we report 2 cases showing different primary origins but presentation in oral cavity being the first symptom. One case is of an 82 year old male with a complaint of swelling in right mandible and a diagnosis of prostatic adenocarcinoma metastasizing to oral cavity was established. The other case presented here is of a 42 year old male with pain and swelling in right mandible. The diagnosis of adenoid cystic carcinoma was made and a full body scan helped in early identification of metastatic deposits in lung. Despite the infrequent occurrence of metastases in oral region, dental surgeon should be aware of the possibilities for correct diagnostic conduction and subsequently, the initiation of treatment in early stages of disease.

Differential tumor gene expression profiling of obese and non-obese patients (pts) with prostatic adenocarcinoma (PC).

5075 Background: Increased baseline body mass index (BMI) has been linked to poorer prostate cancer outcomes, including recurrence, reduced quality of life, and mortality (PMID: 21325564, 17211863). Herein, we sought to interrogate and validate the corresponding differences in tumor gene expression profiles of obese (Ob) vs. non-obese (N-Ob) pts with PC. Methods: In this IRB-approved retrospective study, eligibility criteria included histologically confirmed PC and available RNA sequencing results from treatment naïve primary prostate tissue from a CLIA-certified lab (either Tempus or Caris Life Sciences). Tempus cohort was used for interrogation and Caris for validation. Pts in each cohort were categorized into two groups: obese (BMI≥30) and non-obese (BMI&lt;30). BMI at the time of diagnosis of PC was used for analysis. The DEseq2 pipeline was used to analyze differentially expressed genes between the groups. The data included the Log2 fold change, Wald-Test p-values, and Benjamini-Hochberg adjusted p-values for each differentially expressed gene. These results were subjected to Gene Set Enrichment software analysis (GSEA) to identify pathways enriched in each cohort. All bioinformatic analysis was undertaken using R v4.2. Results: Tempus cohort: n=60 (Ob =22, N-Ob=38); Caris cohort: n=50 (Ob=17, N-Ob=33). Both Tempus and Caris showed that Ob pts had an increased expression of the heme metabolism, androgen response, protein secretion, fatty acid, and bile metabolism pathways. N-Ob pts had a significantly higher expression of genes involved in the inflammation pathways (interferon-alpha &amp; TNF alpha pathways). Normalized enrichment scores are reported in the table. Differential gene set expression analysis in Ob vs. N-Ob pts with PC. Conclusions: Our study showed an upregulation of distinct genomic pathways in Ob pts with prostate cancer. For example, Ob pts with PC have tumors that depend more on androgen signaling, and N-Ob pts' tumors express increased inflammatory pathway genes that promote PC growth, invasiveness, and metastasis. After external validation, these hypothesis-generating data may provide the rationale for personalized therapy in men with PC. [Table: see text]

Gleason Score-related MT1L as biomarker for prognosis in prostate adenocarcinoma and contribute to tumor progression in vitro.

The Gleason Score is well correlated with biological behavior and prognosis in prostate adenocarcinoma (PRAD). This study was derived to determine the clinical significance and function of Gleason-Score-related genes in PRAD. RNA-sequencing profiles and clinical data were extracted from the The Cancer Genome Atlas PRAD database. The Gleason-Score-related genes were screened out by the Jonckheere-Terpstra rank-based test. The "limma" R package was performed for differentially expressed genes. Next, a Kaplan-Meier survival analysis was performed. Correlation MT1L expression levels with tumor stage, non-tumor tissue stage, radiation therapy, and residual tumor were analyzed. Further, MT1L expression was detected in PRAD cell lines by reverse transcription-quantitative polymerase chain reaction assay. Overexpression of MT1L was constructed and used for cell count kit-8, flow cytometric assay, transwell assay, and wound-healing assay. Survival analysis showed 15 Gleason-Score-related genes as prognostic biomarkers in PRAD. The high-frequency deletion of MT1L was verified in PRAD. Furthermore, MT1L expression was decreased in PRAD cell lines than RWPE-1 cells, and overexpression of MT1L repressed cell proliferation and migration, and induced apoptosis in PC-3 cells. Gleason-Score-related MT1L may serve as a biomarker of poor prognostic biomarker in PRAD. In addition, MT1L plays a tumor suppressor in PRAD progression, which is beneficial for PRAD diagnosis and treatment research.

Left supraclavicular Lymphadenopathy as initial presentation of prostate Adenocarcinoma: An unusual presentation of a common cancer

Left supraclavicular lymphadenopathy is an ominous finding of physical examination. An underlying malignancy is found in about 50% of cases. This case report describes a male patient admitted for acute heart failure and respiratory infection. During physical examination a large left supraclavicular mass was identified. There were no symptoms or other findings suggesting malignancy. A full body Computed Tomography (CT) scan imaging revealed generalized lymphadenopathy. The histopathological examination of a cervical lymphadenopathy suggested metastasis of a poorly differentiated carcinoma. Prostate specific antigen level was very high (325 µg/L). The digital rectal examination and prostate biopsy confirmed the diagnosis of prostate adenocarcinoma. Even though this is an uncommon presentation of a very frequent disease, finding a supraclavicular lymphadenopathy in male patients should raise the suspicion of metastatic prostate cancer.

Real world rates of genetic referrals and germline testing in patients with prostate adenocarcinoma at an academic cancer center in southern New Jersey.

114 Background: Prostate adenocarcinoma is the second leading cause of cancer-related death in men in the United States. A major risk factor is family history, with prostate cancer in a first-degree relative effectively doubling a patient’s risk. However, relying on family history alone fails to identify many patients with clinically relevant cancer-related germline mutations, which can have important prognostic and therapeutic implications for patients and their families. In 2018, the NCCN recommended expanding the germline testing to include all men with high risk, very high risk, regional or metastatic prostate cancer. We sought to identify the rate of genetic testing within this patient population at the MD Anderson Cancer Center at Cooper University Hospital. Methods: The institution database was queried to identify patients with the ICD-10 diagnosis of prostate adenocarcinoma between 01-2019 and 12-2020; the inclusion criteria were age 18 years or older, biopsy-proven prostate adenocarcinoma, and qualification to receive germline genetic testing per NCCN guidelines. A total of 201 patients were screened and 97 cases were analyzed. Results: Of the 97 patients who qualified for genetic testing, 53 were referred to genetics (54.6%). 27 of the 53 patients who met with our genetics team underwent testing (50.9%). Of the 27 patients tested, nine patients (33.3%) were found to have clinically relevant cancer-related germline mutations with therapeutic implications for the patient and/or screening recommendations for the patient and their family members. Conclusions: Overall, the proportion of patients who qualified for and completed genetic testing was low at 27.8%. Of those who completed testing, the rate of detection of a significant germline mutation was high at 33.3%, indicating that a significant proportion of those untested may carry a genetic mutation of clinical importance. Based on these results, we developed an electronic Best Practice Alert that notifies providers if a patient qualifies for a genetic risk evaluation based on his prostate cancer risk. We implemented this system, with reported high utilization demonstrating feasibility of this tool. Preliminary data shows improved rates of referral among prostate cancer patients.

Evaluation of a novel transcriptomic tumor signature (PROSTest) as response biomarker for 177Lu-PSMA therapy in advanced prostate cancer.

183 Background: Radionuclide therapy targeting the prostate specific membrane antigen (177Lu-PSMA therapy) has proven to be an effective treatment in men with metastatic castration resistant prostate cancer (mCRPCs). Despite representing a significant therapeutic breakthrough, a critical unmet need in 177Lu-PSMA therapy, is a prognostic biomarker for treatment optimization. Imaging and standard biomarkers have limited value. The PROSTest is a new 27-gene algorithmic signature originally developed for prostate adenocarcinoma diagnosis (0 to 100, positive score ≥20). We hypothesized that PROSTest would be elevated in mCRPCs and could have utility as a biomarker for mCRPC management. Methods: Prospective enrollment of 113 mCRPC for 177Lu-PSMA therapy (KlbB-5338-0302021 study). Pathology, clinical and biomarker data were available as was PSMA-PET/CT. Blood samples were collected for PROSTest prior to therapy. Target genes were isolated and amplified using qPCR. PROSTest scores (0-100) were obtained following algorithmic analysis. Scores were correlated with mCRPC diagnosis and baseline information. Scores and standard clinical measures were evaluated as prognostic factors with survival as endpoint. Mann-Whitney U-test, Kaplan-Meier survival and Cox proportional hazards regression analysis were utilized. All data: median (IQ range). Results: 89 (79%) patients were evaluable. Age was 75 (68-80). Disease characteristics at time of diagnosis included Gleason scores 8-10 (70%) and TMM: T3-T4 tumors (67%), N1 (53%), M1 (45%). At the time of therapy all patients were metastatic and all exhibited PSMA-positive disease. The highest tumor SUVmax was 51 (28-78). PSA levels were 69ng/mL (18-305). The PROSTest score was 89 (81-92). PROSTest scores were weakly correlated with age (r=0.33, p=0.0015) but not with baseline histopathological parameters (e.g., Gleason score, TNM) or pretreatment imaging results (e.g., SUVmax). Twenty-four (27%) patients have perished. Treatment and follow-up (5 months, 3-18) are ongoing. The mOS was 15 months. No factors were associated with death as an outcome except for the PROSTest score. PROSTest scores ≥79 (based on ROC analysis) were associated with significantly increased risk for mortality (HR: 2.9, 95% CI: 1.5-7.4). The mOS was 14 months in patients with pre-therapy PROSTest scores &gt;79 compared to mOS not reached for PROSTest scores &lt;79 ( p=0.02). In the COX model, baseline PROSTest was confirmed to be significantly predictive of death despite therapy (β = 1.51, p=0.01). Conclusions: The PROSTest blood gene expression score is elevated in mCRPCs. Levels are not associated with baseline clinical, histopathological, pretreatment PSA or imaging parameters. Elevated expression (≥79) of this biomarker prior to treatment was associated with a lower survival and could be used to predict survival in patients undergoing 177Lu-PSMA.

Relationship between Clinicohistomorphology Profile of Atypical Prostate Gland and Diagnosis Benign Lesion or Prostate Adenocarcinoma

BackgroundAtypical prostate gland especially atypical small acinar proliferation (ASAP) is a histopathological diagnosis that requires a follow-up biopsy 3-6 months after the first biopsy, because 17-60% of cases potentially to be malignant. The varied clinical and histomorphological characteristics of the atypical prostate gland make it difficult to confirm the final diagnosis as a benign lesion or prostate adenocarcinoma. This study aims to describe clinicohistomorphological cases of atypical prostate gland at Anatomical Pathology Department FKUI/RSCM and to identify histomorphological features of the atypical prostate gland as benign lesions or prostate adenocarcinoma on immunohistochemistry diagnosis.MethodsA histopathological investigation of prostate gland cases with atypical nuclei was carried out in 2011-2021 from archives of Anatomical Pathology Department FKUI/RSCM. Clinical and histomorphological characteristics were assessed and categorized into benign lesions or prostate adenocarcinoma based on immunohistochemistry appearance.ResultsThere were 109 cases of atypical prostate gland, 49 of which met the inclusion and exclusion criteria and could be analyzed. Corpora amylacea was found in 11 cases (84.6%) in the benign lesion group, statistically significant (p-value 0.005). Intraluminal crystalloids were found in 4 cases (100%) in the prostate adenocarcinoma group with p-value 0.050, close to significant. Other clinicohistomorphological characteristics did not show a significant relationship both in benign lesions and prostate adenocarcinoma groups (p-value 0.05).Conclusion On histopathological examination of the atypical prostate gland that is difficult to re-biopsy, the discovery of corpora amylacea may lead to the diagnosis of a benign lesion, while the discovery of intraluminal crystalloids may lead to the diagnosis of prostate adenocarcinoma. The diagnosis must be supported by immunohistochemistry characteristics.

What can hide an enlarged lymph node of a patient with prostatic adenocarcinoma?

Introduction. Adenocarcinoma is the most common prostatic malignancy where clinical management, Gleason score and recent updates in prostate cancer staging play critical role. Mantle cell lymphoma originates from malignant transformation of B lymphocyte in the outer edge of lymph node follicle, with pathognomonic overexpression of cyclin D1. We present a rare case of two neoplasms occurred in the same individual person. Case report. In a 68-year-old patient planned for radical prostatectomy during the hospital preoperative examinations using multislice computed tomography tumor mass confined to the prostate but also excessive lymph node enlargement were revealed. Tissue specimens were analyzed after using hematoxylin and eosin staining, as well as immunohistochemical biomarker panel. Having performed a thorough histological examination, a diagnosis of prostatic adenocarcinoma, Gleason score 3+4=7, ISUP GG2, was given. Microscopic analysis of lymph node involvement showed unexpected, diffuse proliferation of small lymphoid cells, with irregular nuclei, wide mantle zone and hyalinized blood vessels. After using immunohistochemical staining for specific markers, another diagnosis was set, and it was non Hodgkin mantle cell lymphoma. Conclusion. A prostatic adenocarcinoma can extremely rarely be in a coexistence with undiagnosed lymphoproliferative disease, such as non Hodgkin mantle cell lymphoma in our case.

CD47 (don't eat me signal) expression levels and its relationship with clinicopathologic features in early-stage prostate carcinoma.

Prostate cancer is a cancer with poor host immune response and could be defined as a non-T-cell inflamed tumor. Therefore, immunotherapy treatments could not be included in the treatment of prostate cancer until recently. Inadequate antitumoral response is one of the main reasons why tumor cells multiply rapidly and cause lethal results. It was shown that CD47 molecule, which is secreted at high levels by leukemia cells, reduces macrophage-mediated phagocytosis and thus facilitates escape from the antitumoral immune response. The aim of this study was to show don't eat me signaling in prostate carcinoma tissues and its relationship with macrophage polarization. A total of 263 patients with a diagnosis of prostatic adenocarcinoma after radical prostatectomy between 2015 and 2020 at our institute were included in the study. CD47, CD68, and CD163 expression levels were examined immunohistochemically (IHC)in these tissues. The relationship of these expression levels with unfavorable prognostic factors and survival for prostate carcinoma was investigated. In this study, all the operated prostate carcinoma cases had CD47 expression in tumor tissue, but only 52.5% had a high level of expression. Of 263 prostate cancer tissues, 135 (51.3%) showed high expression of CD68 protein and 189 (71.9%) showed high expression of CD163 protein. There was a statistically strong relationship between CD47, CD68, and CD163. The CD47 molecule is basically a molecule that inhibits macrophage activation. CD68 is mostly used for macrophage classification, while CD163 is used for tumor-associated macrophage classification. Unlike others, we IHCexamined CD47, CD68, and CD163 expressions in the surgical materials of patients who were operated for prostate carcinoma. In addition, we concluded that strong CD47 expression was closely associated with strong CD68 and CD163 expression in all tumor samples. However, a significant relationship between these expression levels and survival could not be demonstrated.

Predictive value of CCR3 expression on diagnosis and prognostic classification of the Prostate Adenocarcinoma

Objective: Chemokines are factors secreted from damaged or infected tissues to induce an inflammatory and immunological reaction. Approximately Chemokines have recently been found to be secreted by most cancer cells. The aim of this study is to compare the CCR-3 expression with the clinicopathological variables in patients with prostatic adenocarcinoma(PCa) and benign prostatic hyperplasia(BPH). Material Method: The study included 25 patients with PCa who underwent prostatectomy, 25 patients with BPH. In the study, CCR-3 expression in PCa and BPH tissues was examined by immunohistochemical method, and CCR-3 expression at PCA and BPH tissues was compared with normal prostate tissue at mRNA level by the Real-Time PCR. Results: CCR-3 expression was found to be significantly higher in PCa patients (p=0,001). There was no relationship between Gleason prognostic grade and periprostatic spread and CCR-3 expression (p=0,887, p=0,279). A statistically significant increase was found in total PSA and CCR-3 expression (p=0,001). Conclusion: In prostate cancer, expression of the CCR3 receptor is associated with the occurrence of aggressive disease with extended local dissemination and a higher risk of biochemical recurrence. According to this study, the CCR-3 expression may be useful in predicting the diagnosis of PCa and there was a significant relationship between total PSA. The Increasing total PSA was also correlation to increased of the CCR3 expression. However, there was no significant relationship between Gleason prognostic grade.

Multitarget Molecular Imaging in Metastatic Castration Resistant Adenocarcinoma Prostate Cancer with Therapy Induced Neuroendocrine Differentiation.

Neuroendocrine differentiation of prostate cancer (NEDPC) includes de novo presentation and secondary to epigenetic changes, referred as therapy-induced neuroendocrine prostate cancer (t-NEPC). Molecular imaging with prostate-specific membrane antigen (PSMA) and somatostatin analogues positron emission tomography (PET/CT) in NEDPC have not been validated. 18F-FDG (fluorodeoxyglucose) PET/CT has numerous limitations in prostate cancer (PCa) and the utility in NEDPC has only been reported in a few series of cases. The objective of this study is to compare the lesions detection rate of the three radiotracers in metastatic t-NEPC patients. (1) Material and Methods: Retrospective evaluation of patients with prostate adenocarcinoma treated with androgen deprivation therapy, chemotherapy, a novel androgen receptor pathway inhibitor or a combination of them and a second tumour biopsy confirming t-NEPC was made. All patients underwent 18F PSMA-1007, 18F AlF-NOTA-Octreotide, and 18F-FDG PET/CT. Evaluation of positive lesions was determined and SUVmax of each radiotracer was estimated and correlated with computer tomography (CT) findings. (2) Results: A total of eight patients were included. The mean time from diagnosis of prostate adenocarcinoma to t-NEPC was 28.2 months, with a mean serum specific prostate antigen (PSA) of 16.6 ng/dl at the time of NEPC diagnosis. All patients were treated with antiandrogen therapy and 87.5% with chemotherapy. A total of 273 lesions were identified by CT from which 182 were detected by 18F-FDG PET/CT, 174 lesions by 18F PSMA-1007, and 59 by 18F AlF-NOTA-Octreotide. An interpatient analysis of the lesions was performed and dual tracer 18F-FDG PET/CT and 18F PSMA-1007 PET/CT detected a total of 270/273 lesions (98.9%). (3) Conclusions: NEDPC patients demonstrated wide inter and intrapatient molecular imaging heterogeneity within the three radiotracers. 18F-FDG detected most lesions in t-NEPC among all radiotracers, especially in visceral sites; 18F PSMA-1007 detected more bone lesions. 18F AlF-NOTA-Octreotide showed no significant utility.

Copy number variation of urine exfoliated cells by low-coverage whole genome sequencing for diagnosis of prostate adenocarcinoma: a prospective cohort study.

BackgroundNon-invasive, especially the urine-based diagnosis of prostate cancer (PCa) remains challenging. Although prostate cancer antigen (PSA) is widely used in prostate cancer screening, the false positives may result in unnecessary invasive procedures. PSA elevated patients are triaged to further evaluation of free/total PSA ratio (f/t PSA), to find out potential clinically significant PCa before undergoing invasive procedures. Genomic instability, especially chromosomal copy number variations (CNVs) were proved much more tumor specific. Here we performed a prospective study to evaluate the diagnostic value of CNV via urine-exfoliated cell DNA analysis in PCa.MethodsWe enrolled 28 PSA elevated patients (≥ 4 ng/ml), including 16 PCa, 9 benign prostate hypertrophy (BPH) and 3 prostatic intraepithelial neoplasia (PIN). Fresh initial portion urine was collected after hospital admission. Urine exfoliated cell DNA was analyzed by low coverage Whole Genome Sequencing, followed by CNV genotyping by the prostate cancer chromosomal aneuploidy detector (ProCAD). CNVs were quantified in absolute z-score (|Z|). Serum free/total PSA ratio (f/t PSA) was reported altogether.ResultsIn patients with PCa, the most frequent CNV events were chr3q gain (n = 2), chr8q gain (n = 2), chr2q loss (n = 4), and chr18q loss (n = 3). CNVs were found in 81.2% (95% Confidence Interval (CI) 53.7–95.0%) PCa. No CNV was identified in BPH patients. A diagnosis model was established by incorporating all CNVs. At the optimal cutoff of |Z|≥ 2.50, the model reached an AUC of 0.91 (95% CI 0.83–0.99), a sensitivity of 81.2% and a specificity of 100%. The CNV approach significantly outperformed f/t PSA (AUC = 0.62, P = 0.012). Further analyses showed that the CNV positive rate was significantly correlated with tumor grade. CNVs were found in 90.9% (95% CI 57.1–99.5%) high grade tumors and 60.0% (95% CI 17.0–92.7%) low grade tumors. No statistical significance was found for patient age, BMI, disease history and family history.ConclusionsUrine exfoliated cells harbor enriched CNV features in PCa patients. Urine detection of CNV might be a biomarker for PCa diagnosis, especially in terms of the clinically significant high-grade tumors.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12920-022-01253-5.

A CASE REPORT ON PROSTATIC ADENOCARCINOMA WITH MUCINOUS FEATURES

We present a case of primary adenocarcinoma of the prostate with mucinous feature. Mucinous adenocarcinoma (MC) of the pros¬tate gland is rare morphological variant of Prostate carcinoma characterized by pools of extracellular mucin in &gt;25% of tumor. A 72-year-old male presented to our hospital with urinary frequency, nocturia and voiding difculties;on digital rectal examination enlarged prostate was observed without any palpable nodule. on Ultrasonography hypoechoic lesion was observed in left lobe of prostate suggestive of prostate tumor. A transurethral resection of prostate conrmed the diagnosis of Prostatic adenocarcinoma with mucinous features and Gleasons score 9(4+5). We report the cases due to the aggressive beahviour and uncommon diagnosis of mucinous variant of adenocarcinoma of the prostate. But it is seen that its proper diagnosis and treatment signicantly contribute to favourable prognosis.