Faculty of Medicine

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Incidental prostate cancer in patients undergoing radical cystoprostatectomy in treatment for bladder cancer: our five-year results
(SHMSHM - AAMD, 2013)
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Dohchev, S
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The aim of the paper was to verify the incidence and features of incidental prostate cancer in patients who underwent radical cystoprostatectomy for invasive bladder cancer. Methods and results: A total of 96 patients underwent radical cystoprostatectomy between January 2006 and December 2010 in the University Clinic of Urology in Skopje. 10 patients were excluded for incomplete data. The average age of the study group was 61.2 years (range 32-78). Prostate cancer was found in 10 (11.6%) cases. Seven patients were clinically insignificant. Conclusion: Incidentally diagnosed prostate cancer was frequently insignificant. Digital rectal examination and prostate specific antigen should be part of the diagnostic procedure in patients who undergo cystoprostatectomy. Standard RCP which include removal of bladder with prostate gland and seminal vesicles is safer for radicality and prevention of residual prostate cancer.
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Comparative Proteomics Analysis of Urine Reveals Down-Regulation of Acute Phase Response Signaling and LXR/RXR Activation Pathways in Prostate Cancer
(MDPI AG, 2017-12-29)
Davalieva, Katarina
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Kiprijanovska, Sanja
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Maleva Kostovska, Ivana
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Detecting prostate cancer (PCa) using non-invasive diagnostic markers still remains a challenge. The aim of this study was the identification of urine proteins that are sufficiently sensitive and specific to detect PCa in the early stages. Comparative proteomics profiling of urine from patients with PCa, benign prostate hyperplasia, bladder cancer, and renal cancer, coupled with bioinformatics analysis, were performed. Statistically significant difference in abundance showed 20 and 85 proteins in the 2-D DIGE/MS and label-free LC-MS/MS experiments, respectively. In silico analysis indicated activation, binding, and cell movement of subset of immune cells as the top affected cellular functions in PCa, together with the down-regulation of Acute Phase Response Signaling and Liver X Receptor/ Retinoid X Receptor (LXR/RXR) activation pathways. The most promising biomarkers were 35, altered in PCa when compared to more than one group. Half of these have confirmed localization in normal or PCa tissues. Twenty proteins (CD14, AHSG, ENO1, ANXA1, CLU, COL6A1, C3, FGA, FGG, HPX, PTGDS, S100A9, LMAN2, ITIH4, ACTA2, GRN, HBB, PEBP1, CTSB, SPP1) are oncogenes, tumor suppressors, and multifunctional proteins with highly confirmed involvement in PCa, while 9 (AZU1, IGHG1, RNASE2, PZP, REG1A, AMY1A, AMY2A, ACTG2, COL18A1) have been associated with different cancers, but not with PCa so far, and may represent novel findings. LC-MS/MS data are available via ProteomeXchange with identifier PXD008407.
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PROSTATE CANCER AND BENIGN PROSTATE CHANGE – ARE THERE DIFFERENCES IN DEMOGRAPHIC AND BEHAVIOR CHARACTERISTICS?
(Faculty of Medicine, Ss. Cyril and Methodius University in Skopje, 2023-06)
Trifunovski A
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Dohcev S
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Janchulev J
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Prostate cancer (CaP) is one of the major causes of cancer-related mortality worldwide. The incidence rate increases up to 1 in every 52 men aged 50 - 59 years. The variability in distribution is due to the demographic, behavior, and genetic differences, as well as the lifestyle and the health system quality. The aim of this study was to present and compare the demographic and behavior characteristics of patients with malignant and benign prostate change. This was a prospective clinical study, conducted during 2018-2020, at the University Clinic for Urology, Clinical Centre “Mother Teresa”, Skopje, Republic of North Macedonia. The study analyzed 90 patients with prostate cancer (CaP), and 106 patients with benign prostate change (BeP). The average age of patients from CaP/ BeP group was 69.2 ± 6.9 vs. 68.4 ± 6.3 years (p = 0.3696). No significant difference was found in patients from both groups related to BMI (p=0.3009), nutritional status (p=0.4634), smoking status (p=0.4831), clinical symptoms (p=0.6951). Patients in CaP group had 2.83 times more history of father with prostate cancer, for OR = 2.83 [95% CI (1.03-7.83)], and 12.11 times significantly more close family members with other malignancies than those in the BeP group, for OR=12.11 [95% CI (2.71-54.02)]. We need more extensive research in this field, having in mind the multiethnic aspect which will help us in more effective prevention and early diagnosis of prostate cancer in our country.
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Diagnostic performance of prostate health index(PHI) in predicting prostate cancer on prostate biopsy; a single center study.
(Macedonian Association of Anatomists and Morphologists, 2023-12)
Toni Krstev
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Ivica Stojanoski
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Lazar Ilievski
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Nerhim Tufekchioski
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The Prostate Health Index (PHI) is a new test combining total, free and (-2)proPSA into a single score. It was recently approved by the FDA and is now commercially available in the U.S., Europe and Australia. Our aim is to investigate whether PHI improves specificity for detecting clinically significant prostate cancer and can help to reduce prostate cancer biopsies. We examined 100 men age 50 years or older with prostate specific antigen 4 to 10 ng/ml („gray zone„) and normal digital rectal examination with suspected prostate cancer who had undergone biopsies and were divided into a benign and malignant group. In this population we compared the performance of prostate specific antigen, % free prostate specific antigen, (-2)proPSA and PHI to predict biopsy results and, specifically, the presence of clinically significant prostate cancer using multiple criteria. We found statistically significantly increased levels of −2proPSA, PHI and PSA and decreased levels of %freePSA in patients diagnosed with prostate cancer by prostate biopsy vs. patients with benign prostatic conditions (median values: −2proPSA: 28.3 vs. 20.11 ng/l, PHI: 73.04 vs. 30.5, total PSA: 7.3 vs. 6.48 ng/ml and %free PSA: 17.06 vs. 25.62%). On receiver operating characteristic analysis PHI had the highest AUC for overall prostate cancer (AUCs PHI 0.954, percent free prostate specific antigen 0.345, (-2)proPSA 0.753 and prostate specific antigen 0.656). The optimal cut-off for PHI in the study population was 42.8 with sensitivity of 85.7% (95% CI: 54.8-90.6) and specificity of 86.1% (CI 95%, 0.913-0.995). Whereas, in the tPSA for cut-off 6.54 sensitivity is 61.9 and specificity 59.5, respectively. The Prostate Health Index was significantly higher in men with Gleason 7 or greater. In our study for the PHI levels (36-54.99) only 23.08% of patients had Gleason score ≥ 7.In patients with PHI levels >55, 76.92% of patients had Gleason score ≥ 7. The new PHI test outperforms its individual components of total, free and (-2)proPSA for the identification of clinically significant prostate cancer. PHI may be useful as part of a multivariable approach to reduce prostate biopsies and overdiagnosis.
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Potential Role of Seven Proteomics Tissue Biomarkers for Diagnosis and Prognosis of Prostate Cancer in Urine
(MDPI AG, 2022-12-16)
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Rusevski, Aleksandar
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Popov, Zivko
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<jats:p>As the currently available tests for the clinical management of prostate cancer (PCa) are still far from providing precise diagnosis and risk stratification, the identification of new molecular marker(s) remains a pertinent clinical need. Candidate PCa biomarkers from the published proteomic comparative studies of prostate tissue (2002–2020) were collected and systematically evaluated. AZGP1, MDH2, FABP5, ENO1, GSTP1, GSTM2, and EZR were chosen for further evaluation in the urine of 85 PCa patients and controls using ELISA. Statistically significant differences in protein levels between PCa and BPH showed FABP5 (p = 0.019) and ENO1 (p = 0.015). A biomarker panel based on the combination of FABP5, ENO1, and PSA provided the highest accuracy (AUC = 0.795) for PCa detection. The combination of FABP5, EZR, AZGP1, and MDH2 showed AUC = 0.889 in PCa prognosis, with 85.29% of the samples correctly classified into low and high Gleason score (GS) groups. The addition of PSA to the panel slightly increased the AUC to 0.914. AZGP1, FABP5, and EZR showed significant correlation with GS, stage, and percentage of positive biopsy cores. Although validation using larger patient cohorts will be necessary to establish the credibility of the proposed biomarker panels in a clinical context, this study opens a way for the further testing of more high-quality proteomics biomarkers, which could ultimately add value to the clinical management of PCa.</jats:p>

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