Alpha-methylacyl-CoA Racemase and Hepsin as Urinary Prostate Cancer Markers

2015 ◽  
Vol 30 (4) ◽  
pp. 401-406 ◽  
Author(s):  
Wiktor Dariusz Sroka ◽  
Marek Adamowski ◽  
Piotr Słupski ◽  
Joanna Siódmiak ◽  
Piotr Jarzemski ◽  
...  

Background Because of the numerous limitations of prostate-specific antigen (PSA), α-methylacyl-CoA racemase (AMACR) and hepsin have recently been suggested as potential biomarkers in prostate cancer (PC). This report presents a comparison study of the presence of AMACR and hepsin in urine collected before and after digital rectal examination (DRE) as a previously suggested diagnostic marker for PC. Methods Seventy-six urine samples (38 before and 38 after prostate massage) from patients with benign prostate hyperplasia (BPH) and 66 urine samples (33 before and 33 after prostate massage) from patients with PC were analyzed. PC was confirmed by prostate biopsy. Urinary levels of AMACR and hepsin were determined by ELISA and related to the tumor stage, Gleason score and PSA level. Results AMACR and hepsin levels in urine collected after prostate massage were higher only in the PC group. There were no correlations between AMACR levels, hepsin levels, tumor stage and Gleason score. AMACR and hepsin did not differentiate between BPH and PC with better true positive and false negative rates than serum PSA. Conclusions AMACR and hepsin were unable to diagnose PC with better true positive and false negative rates than PSA. An additional procedure combined with other markers should be applied for the reliable diagnosis of PC.

2018 ◽  
Vol 5 (6) ◽  
pp. 2059
Author(s):  
Ehab Jasim Mohammad

Background: Prostate cancer is the most common cancer and the second leading cause of cancer-related death among men of western countries. The aim of this study is to develop non-invasive diagnostic tools for the early detection of prostate cancer (PCa) through detection of low level of Serum reduced Glutathione (GSH).Methods: Serum samples from men being evaluated for PCa were analyzed for reduced Glutathione (GSH) level. The results were compared with the prostate needle biopsy findings and (PSA) level combined with Digital Rectal Examination (DRE). Samples were obtained from 59 cases including 18 controls.Results: The maximum sensitivity of the test was observed in the first category of confirmed cases with 93.33% turs positive detected with low GSH. Among those highly suspected Ca prostate there was 87.5% true positive test and 12.5% false negative results. Among those in grey zone where PSA between is 4 and 10, and DRE is suggestive, the proportion of true positive was 50%.Conclusions: These results demonstrate that serum reduced Glutathione (GSH) level is helpful in patient with definite carcinoma. This test could be useful in augmenting current PCa diagnostic procedures. For example, the examination test for reduced Glutathione (GSH) level with an elevated prostate- specific antigen level might be used in predicting which patients will have negative biopsies and may be used as treatment modality for PCa.


2016 ◽  
Vol 2 (3) ◽  
pp. 106-111
Author(s):  
Elena V Bocan ◽  
Ovidiu Mederle ◽  
Marius Raica

El cáncer de próstata es la malignidad más frecuente en los seres humanos en la actualidad. Los estudios post mortem hacen una estimación que el carcinoma de próstata (PCa) se propagará en 25% de los hombres con enfermedad establecida histológica-mente. Material y método: Se ha hecho una investigación retrospectiva sobre la expresión inmune histoquímica de antígeno prostático específico (PSA) en 84 pacientes ingresados en el hospital con sospecha clínica de cáncer de próstata. Fueron examinadas portaobjetos del archivo de biopsia de resección transuretral, biopsia por punción con aguja hueca y cirugía abierta. Portaobjetos tenidos fueron utilizados para el diagnóstico patológico y para la puntuacion de Gleason. Portaobjetos adicionales fueron tenidos para antígeno prostático específico y la reacción final del producto fue estimado en negativo (0), bajo/moderado positivo (+1) y positivo intenso (+2). Resultados: Hiperplasia benigna próstata  fue encontrado en 14 casos, y todos mostraron una reacción moderada /intensa para el antígeno prostático específico. Hiperplasia asociada basal de células fue siempre negativa. Carcinoma fue encontrado en 68 pacientes. La reacción inmune para antígeno prostático específico fue positiva en 88.2% casos, y encontramos una relación directa entre la intensidad de la reacción y la puntuacion de Gleason. Todas las carcinomas uroteliales y pequeñas fueron negativas. La reacción PSA ha detectado 39.68 % de los casos con invasión perineural en comparación con solamente 23.8% encontrado en los portaobjetos tenidos hematoxilina-eosina (H&E). La expresión inmune antígeno prostático específico no discrimina entre lesiones benignas atípicas y el carcinoma  bien diferenciados. Conclusión: Se concluye que la reacción inmune antígeno prostático específico ayuda mucho para el diagnóstico diferenciado, detección de la invasión perineural, y el metástasis ganglionar.  Prostate cancer is the most frequent malignancy in human nowadays. Postmortem studies estimate that prostate carcinoma (PCa) will spread in only 25% of men with histologically defined disease. Material and method: It was retrospectively investigated the immunohistochemical expression of prostate-specific antigen (PSA) in 84 patients admitted with clinical suspicion of prostate cancer. Slides were performed from archive biopsies taken by transurethral resection, core biopsy and open surgery. Routine stained slides were used for the pathologic diagnosis and Gleason score. Additional slides were stained for PSA, and the final reaction product was estimated as negative (0), weak/moderate positive (+1), and intense positive (+2). Results: Benign prostate hyperplasia was found in 14 cases, and all showed moderate/intense reaction for PSA. Associated basal cell hyperplasia was always negative. Carcinoma was found in 68 patients. The immunoreaction for PSA was positive in 88.2% cases, and we found a direct relationship between the intensity of the reaction and Gleason score. All urothelial and small carcinomas were negative. PSA immunoreaction detected 39.68% cases with perineural invasion as compared with only 23.8% found on hematoxylin-eosin (H&E) stained slides. PSA immunoexpression does not discriminate between atypical benign lesions and well-differentiated carcinoma. Conclusion: It is concluded that PSA immunoreaction is helpful for the differential diagnosis, detection of the perineural invasion, and lymph node metastases. 


2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 217-217
Author(s):  
John Thomas Helgstrand ◽  
Nina Klemann ◽  
Birgitte Grønkaer Toft ◽  
Ben Vainer ◽  
Klaus Brasso ◽  
...  

217 Background: Prostate specific antigen (PSA) based screening increases the number of men diagnosed with early localized prostate cancer (PCa). Further, curatively intended therapies have been demonstrated to reduce PCa mortality in randomized trials. However, controversy exists, and the overall impact on PCa mortality is less clear. Men who eventually die from PCa may constitute a subgroup with either adverse histopathological characteristics and/or clinically advanced disease at diagnosis. However, the clinical characteristics at diagnosis for men who eventually die from PCa are largely unknown. We retrieved clinical characteristics of all men dying from PCa in Denmark in an 18-year period. Methods: All men who died of PCa during the period 1995 to 2013 were identified in the Danish Causes of Death Registry. Age, Gleason score (GS), tumor stage classification, and PSA were retrieved from the Danish Prostate Cancer Registry (DaPCaR). For validation, manual revision of patient charts was performed. Patients were divided into three clinical phenotypes: distant metastatic disease, locally advanced/N+ disease, and localized disease. Patients with localized disease were further grouped according to GS and PSA. Results: A total of 19,487 men died of PCa in the period 1995-2013. In total, 46.7%, 16.8% and 25.1% of men presented with distant metastatic disease, locally advanced/N+ disease or localized disease, respectively. Among men with localized disease, 85.1% had GS ≥ 7 and only 2.1% (0.5% of all men dying from PCa) only, presented with low risk (PSA < 20 and GS ≤ 6) localized disease at the time of diagnosis. Conclusions: The majority of men (63.5%) who died from PCa had either locally advanced/N+ or M+ disease at diagnosis. Among men with localized PCa at diagnosis, the majority of men subsequently dying from PCa had either PSA > 20 ng/ml and/or adverse histopathological characteristics with Gleason score ≥ 7. A total of 94.5% of patients dying from PCa had either metastatic, locally advanced/N+, and/or GS ≥ 7 disease. Patients with localized disease, PSA < 20 ng/ml and GS ≤ 6 amounted for only 0.5% of all patients dying from PCa.


2014 ◽  
Vol 395 (9) ◽  
pp. 1095-1104 ◽  
Author(s):  
Margaritis Avgeris ◽  
Konstantinos Stravodimos ◽  
Andreas Scorilas

Abstract A large number of prostate cancer (PCa) patients receive treatment without significant benefits, strengthening the need for accurate prognosis, which can be supported by the study of miRNAs. In silico specificity analysis was performed for the identification of miRNAs able to regulate KLK2 and KLK4 expression. Total RNA was extracted from prostate tissues obtained from PCa and benign prostate hyperplasia patients. Thereafter, RNA was polyadenylated and reverse transcribed to cDNA, which was used for qPCR analysis. miR-378 was predicted to target both KLK2 and KLK4 and downregulated levels detected in PCa patients (p=0.050). The reduction of miR-378 was correlated with higher Gleason score (p=0.018), larger diameter tumors (p=0.034), and elevated serum PSA (p=0.006). Regarding prognosis, miR-378 was able to improve risk stratification according to Gleason score or tumor stage, while higher risk to recur highlighted for the patients expressing lower miR-378 levels. Finally, the loss of miR-378 was able to predict the short-term relapse of ‘high’- and ‘very high’-recurrence-risk patients, independent of Gleason score, tumor stage, PSA, and age as indicated by Kaplan-Meier survival curves (p=0.030) and multivariate Cox regression analysis (p=0.018). In conclusion, loss of miR-378 expression increases the risk for PCa progression and relapse, despite active treatment.


2020 ◽  
Vol 4 (1) ◽  
pp. 88-93
Author(s):  
Jin-Qi Song ◽  
Ya-Nan Zhou ◽  
Gang-Liang Tu ◽  
Hui Xu

Background: In recent years, the incidence of prostate cancer (PCa) is increasing. Advanced PCa has a poor prognosis and high cost, which seriously affects the quality of life of patients. Therefore, how to improve the diagnosis rate and prognosis of early PCa is the focus of clinical research. This paper aims to investigate the value of  P504s, 34βE12, Ki-67 and prostate-specific antigen (PSA) in the diagnosis and prognosis of PCa. Objective: To investigate the expression of P504s, 34βE12, Ki67 and PSA in prostate tissues and their clinical significance. Methods: Twenty four cases in the study group were selected from PCa confirmed by pathology in the urology department of Chengde Affiliated Hospital from October 2018 to August 2020, and 33 cases of Benign Prostate Hyperplasia (BPH) confirmed by pathology in the same period were selected as the control group. The expression of P504s, 34βE12 and Ki-67 in prostate tissues were determined by immunohistochemistry. Results: The positive expression rates of P504s, 34βE12 and TPSA or F/TPSA in PCa patients were 95.8%, 12.5% and 87.5%, respectively. The positive rates in BPH patients were 9.1%, 93.9% and 27.3%. The difference between the two groups was statistically significant (p<0.05). PCa bone or lymph node metastasis was positively correlated with Ki-67 (r=0.423, p<0.05) and Gleason score (r=0.446, p<0.05), indicating a stronger correlation with Gleasonscore. Conclusion: The combined detection of P504s, 34βE12 and PSA is helpful for the diagnosis and differential diagnosis of PCa. High Gleason score and ki-67 expression may indicate high risk of PCa metastasis and poor prognosis.


2013 ◽  
Vol 59 (1) ◽  
pp. 306-314 ◽  
Author(s):  
Carsten Stephan ◽  
Sébastien Vincendeau ◽  
Alain Houlgatte ◽  
Henning Cammann ◽  
Klaus Jung ◽  
...  

BACKGROUND Total prostate-specific antigen (tPSA) is flawed for prostate cancer (PCa) detection. [−2]proprostate-specific antigen (p2PSA), a molecular isoform of free PSA (fPSA), shows higher specificity compared with tPSA or percentage of free PSA (%fPSA). The prostate health index (Phi), a measure based on p2PSA and calculated as p2PSA/fPSA × √tPSA, was evaluated in a multicenter study for detecting PCa. METHODS A total of 1362 patients from 4 different study sites who had tPSA values of 1.6–8.0 μg/L (668 patients with PCa, 694 without PCa) underwent ≥10 core biopsies. Serum concentrations of tPSA, fPSA (both calibrated against a WHO reference material), and p2PSA were measured on Access2 or DxI800 analyzers (Beckman Coulter). RESULTS The percentage ratio of p2PSA to fPSA (%p2PSA) and Phi were significantly higher in all PCa subcohorts (positive initial or repeat biopsy result or negative digital rectal examination) (P &lt; 0.0001) compared with patients without PCa. Phi had the largest area under the ROC curve (AUC) (AUC = 0.74) and provided significantly better clinical performance for predicting PCa compared with %p2PSA (AUC = 0.72, P = 0.018), p2PSA (AUC = 0.63, P &lt; 0.0001), %fPSA (AUC = 0.61) or tPSA (AUC = 0.56). Significantly higher median values of Phi were observed for patients with a Gleason score ≥7 (Phi = 60) compared with a Gleason score &lt;7 (Phi = 53; P = 0.0018). The proportion of aggressive PCa (Gleason score ≥7) increased with the Phi score. CONCLUSIONS The results of this multicenter study show that Phi, compared with tPSA or %fPSA, demonstrated superior clinical performance in detecting PCa at tPSA 1.6–8.0 μg/L (i.e., approximately 2–10 μg/L in traditional calibration) and is better able to detect aggressive PCa.


2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 5054-5054
Author(s):  
K. Drewnowska ◽  
E. D. Crawford ◽  
J. Qian ◽  
S. Varvel ◽  
M. Wilk ◽  
...  

5054 Background: Currently, early detection of prostate cancer relies primarily on an abnormal digital rectal examination (DRE) and an elevated prostate-specific antigen (PSA) level leading to a prostate biopsy. However, because of low positive predictive values, up to 75% of men with elevated PSA and/or suspicious DRE have a negative biopsy. We investigated the value of a new molecular marker–PCA3 in predicting the likelihood of prostate cancer. Methods: We undertook a prospective, multi-practice, community-urologist-based, and IRB approved clinical trial to evaluate PCA3. Urine samples were obtained from 974 men with elevated serum PSA (> 2.5ng/ml) and/or abnormal digital rectal examination prior to routine minimum 10-core prostate biopsy following standard study protocol in 30 medical practices. Urine samples were processed within 48 hours of collection. PCA3 and PSA mRNA were isolated, amplified and quantified by magnetic target capture, transcription-mediated amplification, and chemiluminescent hybridization protection assay technologies. The PCA3 value was determined using the ratio of PCA3 mRNA copy number to the PSA mRNA copy number multiplied by 1,000. Results: In total, 380 of 974 patients (39%) were diagnosed with prostate cancer, with a mean Gleason score of 7 (range, 6–9) and 26% (range 1–100%) of the biopsy specimens involved by cancer. An additional 106 cases (11%) had only high-grade PIN and/or atypical small acinar proliferation suspicious for cancer (ASAP), and 488 cases (50%) were benign. The mean PCA3 value in men with prostate cancer was significantly higher than in those without cancer (48 vs. 26, p < 0.0001). PCA3 score was associated with the presence of cancer (p < 0.0001) and Gleason score (p = 0.0001), but was not associated cancer volume (p = 0.56). Using a cutoff value of 35, PCA3 had an odds ratio of 2.6 for predicting prostate cancer. PCA3 had a specificity of 77% and a sensitivity of 44% for the diagnosis of prostate cancer, while the specificity and sensitivity for serum PSA were 22% and 87%, respectively. Conclusions: We found that the PCA3 urine test significantly improved the specificity for the detection of prostate cancer compared to serum PSA. Further evaluation of this urinary marker in screening for prostate cancer appears indicated. No significant financial relationships to disclose.


2018 ◽  
Vol 5 (4) ◽  
pp. 3760-3763
Author(s):  
Zuhirman Zamzami

Purpose: To evaluate the prediction of prostate cancer based on normal digital examination (DRE) and normal prostate specific antigen (PSA) in clinical Benign Prostate Hyperplasia. Materials and Methods: We reviewed medical records of prostate cancer in prostate enlargement patients with urinary retension underwent transurethral resection of the prostate  (TURP) based on  normal DRE, and normal PSA in Arifin Achmad Regional General Hospital, Pekanbaru, Riau Province, Indonesia in January 2010 – Desember 2016. Statistical analysis of univariate was used. Approval on the study was obtained from the Ethical Review Board for Medicine and Health Research, Medical Faculty, University of Riau. Results: There were 644 prostate enlargement patients with urinary retension underwent TURP) in this study in which mostly (51%) in 60-69 year age group,  Most (69.7%) DRE were normal and PSA levels of ≤ 4 ng/ml  were in 122 (19%) patients. There were 19 (18.5%) prostate cancer in patients with normal DRE and PSA. Conclusion: We found there were 19 (18.5%) prostate cancers in prostate enlargement patients with normal DRE and PSA findings as the prediction.


PLoS ONE ◽  
2020 ◽  
Vol 15 (12) ◽  
pp. e0244149
Author(s):  
Yudai Ishiyama ◽  
Masaki Shimbo ◽  
Junpei Iizuka ◽  
Gautam Deshpande ◽  
Kazunari Tanabe ◽  
...  

In addition to breast, ovarian, and pancreatic cancers, BRCA1/2 genes have been associated with prostate cancer (PC). However, the role of BRCA1/2-associated family cancer history (FCH) has remained unexplored in treating these four cancer types as a homogenous pathophysiological group. We aimed to clarify the relationship between BRCA1/2-associated FCH and PC, and to assess its relationship with cancer aggressiveness. Patient characteristics, positive family history of BRCA1/2-associated cancer, and cancer characteristics (Gleason score, prostate specific antigen level at diagnosis, and clinical tumor stage) were analyzed. Among the 1,985 eligible candidates, 473 (23.83%) patients had adequately detailed FCH, obtained via questionnaire, and were thus included in the study. BRCA1/2-associated FCH was observed in 135 (28.54%) patients with PC (68, 14.38%), breast (44, 9.30%), pancreatic (31, 6.55%), or ovarian (8, 1.69%) cancers. BRCA1/2-associated FCH was not significantly associated with high Gleason score (≥ 8). Patients with BRCA-associated FCH were less likely to present with high clinical tumor stage, and no difference was observed in prostate-specific antigen level, presence of metastatic lesions at diagnosis, or likelihood of high-risk classification between patients with and without BRCA-associated FCH. This is the first report of BRCA1/2-associated FCH in Japanese men, indicating that family history did not affect the severity or aggressiveness of PC.


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