Glycomic Approach for Potential Biomarkers on Prostate Cancer: Profiling of N-Linked Glycans in Human Sera and pRNS Cell Lines

Prostate cancer is a leading cause of cancer death among men. Currently available screening test measures prostate-specific antigen (PSA) to detect prostate cancer. However, this test produces false positive values that often lead to negative biopsies. Therefore, a more reliable diagnostic tool is needed. Glycans in serum are of particular interest as around half of all proteins are glycosylated. In this study, N-linked glycans were enzymatically released by PNGase F from prostate epithelial cell lines (pRNS) expressing wild type or mutant androgen receptors and a small set of human serum samples. Released glycans were purified and partitioned into neutral and acidic components by solid phase extraction (SPE) using graphitized carbon cartridges. The SPE fractions were analyzed by matrix-assisted laser desorption/ionization Fourier transform ion cyclotron resonance mass spectrometry (MALDI FT-ICR MS). Significant changes in some high-mannose and fucosylated biantennary complex N-linked glycans were observed in the serum of prostate cancer patients.

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Development of Sensitive Immunoassays for Free and Total Human Glandular Kallikrein 2

Clinical Chemistry ◽

10.1373/clinchem.2004.035253 ◽

2004 ◽

Vol 50 (9) ◽

pp. 1607-1617 ◽

Cited By ~ 36

Author(s):

Ville Väisänen ◽

Susann Eriksson ◽

Kaisa K Ivaska ◽

Hans Lilja ◽

Martti Nurmi ◽

...

Keyword(s):

Prostate Cancer ◽

Detection Limit ◽

Solid Phase ◽

Specific Antigen ◽

Control Group ◽

Serum Samples ◽

Human Kallikrein 2 ◽

Kallikrein 2 ◽

Capture Antibody ◽

Total Psa

Abstract Background: Free and total human kallikrein 2 (hK2) might improve the discrimination between prostate cancer and benign prostatic hyperplasia. Concentrations of hK2 are 100-fold lower than concentrations of prostate-specific antigen (PSA); therefore, an hK2 assay must have a low detection limit and good specificity. Methods: PSA- and hK2-specific monoclonal antibodies were used in solid-phase, two-site immunofluorometric assays to detect free and total hK2. The total hK2 assay used PSA-specific antibodies to block nonspecific signal. The capture antibody of the free hK2 assay did not cross-react with PSA. To determine the hK2 concentrations in the male bloodstream, total hK2 was measured in a control group consisting of 426 noncharacterized serum samples. Free and total hK2 were measured in plasma from 103 patients with confirmed prostate cancer. Results: All 426 males in the control group had a total hK2 concentration above the detection limit of 0.0008 μg/L. The median total hK2 concentration was 0.022 μg/L (range, 0.0015–0.37 μg/L). hK2 concentrations were 0.1–58% of total PSA (median, 3.6%). hK2 concentrations were similar in men 41–50 and 51–60 years of age. The ratio of hK2 to PSA steadily decreased from 5–30% at PSA <1 μg/L to 1–2% at higher PSA concentrations. In 103 patients with prostate cancer, the median hK2 concentration in plasma was 0.079 μg/L (range, 0.0015–16.2 μg/L). The median free hK2 concentration was 0.070 (range, 0.005–12.2) μg/L. The proportion of free to total hK2 varied from 17% to 131% (mean, 85%). Conclusions: The wide variation in the free-to-total hK2 ratio suggests that hK2 in blood plasma is not consistently in the free, noncomplexed form in patients with prostate cancer. The new assay is sufficiently sensitive to be used to study the diagnostic accuracies of free and total hK2 for prostate cancer.

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Aspartyl (Asparaginyl) ß hydroxylase (AABH) as a serum bio-marker for prostate cancer to identify prostate cancer, regardless of PSA level.

Journal of Clinical Oncology ◽

10.1200/jco.2018.36.6_suppl.10 ◽

2018 ◽

Vol 36 (6_suppl) ◽

pp. 10-10

Author(s):

Mahmood Moshiri ◽

Kiarash Moshiri ◽

Arsha Moshiri ◽

Hassan Monhemi ◽

Mohammad Hadi Sekhavati

Keyword(s):

Prostate Cancer ◽

Cancer Patients ◽

Early Stage ◽

Sandwich Elisa ◽

Specific Antigen ◽

High Serum ◽

Cancer Tissue ◽

Serum Samples ◽

Psa Testing ◽

Detect Prostate Cancer

10 Background: Background: Prostate Specific Antigen (PSA) is a molecular marker of prostate cancer (PC). I most countries, standard of care suggests annual PSA testing in all men over 50 years of age; and for men at high risk, the test is recommended from 40 years of age. Due to low Specificity and low sensitivity of the PSA test, a large number of unnecessary biopsies occur every year. This low specificity can be due to the fact that PSA is found in both benign and malignant lesions of Prostate tissue. To date measurement of the percentage of free PSA, have resulted an small improvements in specificity of PSA testing. Thus, the development of a simple blood test to detect prostate cancer that exhibits higher specificity compared to PSA could have the potential of reducing biopsies performed due to false positive screening results and improve the quality of medical care. Methods: We have investigated the utility of aspartyl (asparaginyl) β-hydroxylase (AABH) as a prostate cancer biomarker. AABH has been detected by immunohistochemical staining (IHC) in a broad range of cancers including Prostate Adenocarcinoma through out the world. AABH have been detected by IHC in more than 97% of tumor specimens tested (n > 200) while absent in normal and non cancer tissue. We have developed a sandwich ELISA test for the detection of AABH in serum samples. Preliminary results showed an accuracy of 91- 94% for detecting cancer patients from non-cancer patients in different types of Cancer. Here we have utilized this assay to detect AABH levels in the sera of patients diagnosed with Prostate cancer (biopsy proven, pre-treatment samples), compared to non-cancer individuals. Results: AABH was detected above a threshold level of 1.2 ng/mL in 91% of the sera of PC patients (n = 60), in all different stages and grades of Prostate Cancer. All non-cancer individuals (n = 30) had AABH values below the threshold. Further study of direct comparison of AABH to PSA levels (n = 4,000) is underway. Conclusions: Our data suggest that measurement of serum AABH levels may help to detect Prostate Cancer in early stage and potentially reduce the number of prostate biopsies performed due to increased high serum PSA.

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Quantification of a Proteotypic Peptide from Protein C Inhibitor by Liquid Chromatography–Free SISCAPA-MALDI Mass Spectrometry: Application to Identification of Recurrence of Prostate Cancer

Clinical Chemistry ◽

10.1373/clinchem.2012.199786 ◽

2013 ◽

Vol 59 (10) ◽

pp. 1514-1522 ◽

Cited By ~ 40

Author(s):

Morteza Razavi ◽

Lisa DS Johnson ◽

Julian J Lum ◽

Gary Kruppa ◽

N Leigh Anderson ◽

...

Keyword(s):

Prostate Cancer ◽

Liquid Chromatography ◽

High Throughput ◽

Protein C ◽

Specific Antigen ◽

Serum Concentrations ◽

Serum Samples ◽

Biomarker Validation ◽

Protein C Inhibitor ◽

Proteotypic Peptide

BACKGROUND Biomarker validation remains one of the most challenging constraints to the development of new diagnostic assays. To facilitate biomarker validation, we previously developed a chromatography-free stable isotope standards and capture by antipeptide antibodies (SISCAPA)-MALDI assay allowing rapid, high-throughput quantification of protein analytes in large sample sets. Here we applied this assay to the measurement of a surrogate proteotypic peptide from protein C inhibitor (PCI) in sera from patients with prostate cancer. METHODS A 2-plex SISCAPA-MALDI assay for quantification of proteotypic peptides from PCI and soluble transferrin receptor (sTfR) was used to measure these peptides in 159 trypsin-digested sera collected from 51 patients with prostate cancer. These patients had been treated with radiation with or without neoadjuvant androgen deprivation. RESULTS Patients who experienced biochemical recurrence of prostate cancer showed decreased serum concentrations of the PCI peptide analyte within 18 months of treatment. The PCI peptide concentrations remained increased in the sera of patients who did not experience cancer recurrence. Prostate-specific antigen concentrations had no predictive value during the same time period. CONCLUSIONS The high-throughput, liquid chromatography–free SISCAPA-MALDI assay is capable of rapid quantification of proteotypic PCI and sTfR peptide analytes in complex serum samples. Decreased serum concentrations of the PCI peptide were found to be related to recurrence of prostate cancer in patients treated with radiation with or without hormone therapy. However, a larger cohort of patients will be required for unequivocal validation of the PCI peptide as a biomarker for clinical use.

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Streptavidin-Polyvinylamine Conjugates Labeled with a Europium Chelate: Applications in Immunoassay, Immunohistochemistry, and Microarrays

Clinical Chemistry ◽

10.1093/clinchem/46.9.1450 ◽

2000 ◽

Vol 46 (9) ◽

pp. 1450-1455 ◽

Cited By ~ 46

Author(s):

Andreas Scorilas ◽

Anders Bjartell ◽

Hans Lilja ◽

Christina Moller ◽

Eleftherios P. Diamandis

Keyword(s):

Solid Phase ◽

Specific Antigen ◽

Microarray Experiment ◽

Immunohistochemical Localization ◽

Macromolecular Complex ◽

Serum Samples ◽

Time Resolved ◽

Europium Chelate ◽

Highly Correlated ◽

Detection Reagent

Abstract Background: The favorable properties of lanthanide chelates compared with conventional fluorescent probes have attracted considerable interest. A Eu3+ chelator, 4,7-bis(chlorosulfophenyl)-1,10-phenanthroline-2,9-dicarboxylic acid (BCPDA), has been synthesized previously. Methods: We here describe immunoassay, immunohistochemistry, and microarray applications of a new streptavidin-based universal polyvinylamine (PVA) detection reagent that is multiply labeled with the europium chelate of BCPDA. Solid-phase time-resolved immunofluorometric assays for biotinylated mouse IgG and prostate-specific antigen (PSA) were developed using the new conjugate as a detection reagent. The new conjugate was also used for the immunohistochemical localization of PSA expression in paraffin-embedded prostatic tissues. A model microarray with spotted biotinylated antibody as target was also performed. Results: Approximately 50–100 BCPDA moieties were covalently bound to PVA, which was then linked to streptavidin via biotin interaction. The macromolecular complex successfully recognized and bound biotinylated detection reagents, e.g., antibodies. The new reagent enabled measurement of solid phase-immobilized biotinylated mouse IgG with a detection limit of ∼1 pg/assay and demonstrated excellent linearity. In an ELISA-type sandwich PSA assay that included two PSA monoclonal antibodies using the new conjugate as detection reagent, we detected 0.001 μg/L PSA (∼100 fg or ∼3 amol/assay). Serum samples analyzed for PSA by this method and a commercial assay gave highly correlated results. The new reagent enabled excellent immunohistochemical localization of PSA expression in prostate tissues. Using the new reagent in a model microarray experiment with biotinylated mouse IgG as target, we demonstrated excellent spatial resolution of 5- to 10-nL microspots. Conclusions: The new detection reagent may find important applications in biotechnology.

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Measurement of Prostate-specific Antigen by Use of a Novel Blood Collection and Analytical System

Clinical Chemistry ◽

10.1093/clinchem/48.8.1272 ◽

2002 ◽

Vol 48 (8) ◽

pp. 1272-1278 ◽

Cited By ~ 4

Author(s):

Barbara R Grzeda ◽

Tuan Le Bui ◽

Cheryl N Warner ◽

Tracy L Pirucki ◽

Lisa M Dewey ◽

...

Keyword(s):

Prostate Cancer ◽

Prostate Specific Antigen ◽

Whole Blood ◽

Prostate Cancer Screening ◽

Specific Antigen ◽

Blood Collection ◽

Serum Samples ◽

Stabilizing Solution ◽

Professional Assistance ◽

Comparison Of The Results

Abstract Background: Prostate-specific antigen (PSA) is widely used in the detection and monitoring of prostate cancer. We developed a system for the self-collection and transport of capillary whole blood for PSA analysis, with the goal of reducing phlebotomy visits and, thus, increasing the access and utilization of PSA in prostate cancer screening and monitoring. Methods: The blood collection device [BIOSAFE Blood Transport System (BTSTM)] collects 70 μL of blood through a heparin-coated material into 200 μL of stabilizing solution. The diluted whole blood is used for measurement of PSA by a modified version of the Hybritech® Tandem-MP PSA Assay. Results were compared for matched samples of professionally and self-collected BTS blood and for matched BTS samples sera from blood collected by venipuncture. Imprecision for the whole-blood PSA measurement was estimated from analysis of whole-blood controls in duplicate, twice per day, over 20 days. Results: BTS samples (n = 140) collected by a qualified healthcare professional compared with serum samples yielded the regression equation: y =1.02x + 0.04 (Sy|x = 0.35; r = 0.99). Comparison of the results for samples (n = 128) collected by the patient without professional assistance with serum samples yielded: y = 1.08x + 0.02 (Sy|x = 0.31; r = 0.99). The between-run CVs at 0.069, 0.53, 2.9, and 10.7 μg/L were 21%, 6.0%, 3.5%, and 3.8%, respectively. PSA was stable in BTS samples stored for 21 days at 18–24 °C and for 7 days at 37 °C. Conclusion: The BIOSAFE BTS system allows accurate and convenient measurement of circulating PSA by a precise method for diluted whole blood.

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Discordant prostate specific antigen test results despite WHO assay standardization

The International Journal of Biological Markers ◽

10.1177/1724600818754750 ◽

2018 ◽

Vol 33 (3) ◽

pp. 275-282 ◽

Cited By ~ 2

Author(s):

Martin Boegemann ◽

Christian Arsov ◽

Boris Hadaschik ◽

Kathleen Herkommer ◽

Florian Imkamp ◽

...

Keyword(s):

Prostate Cancer ◽

Early Detection ◽

Specific Antigen ◽

Test Results ◽

Serum Samples ◽

Prostate Specific Antigen Test ◽

Free Psa ◽

Prostate Biopsies ◽

Cancer Early Detection ◽

Total Psa

Introduction: Total PSA (tPSA) and free PSA (fPSA) are the most commonly used biomarkers for early detection of prostate cancer. Despite standardization efforts, many available PSA assays may still produce discordant results. In the present study, we compared four PSA assays calibrated to the WHO standards 96/670 and 96/668 for tPSA and fPSA, respectively. Methods: Within the scope of the Prostate Cancer Early Detection Study Based on a ‘‘Baseline’’ PSA Value in Young Men (PROBASE), we tested tPSA and fPSA in serum samples from 50 patients in the four different PROBASE sites using four WHO-calibrated assays from Roche (Elecsys, Cobas), Beckman-Coulter (Access-II) and Siemens (ADVIA Centaur). The comparison was performed using the Passing–Bablok regression method. Results: Compared to Access, the median tPSA levels for Centaur, Elecsys, and Cobas were +3%, +11%–20%, and +17%–23%, respectively, while for median fPSA levels the differences for Centaur, Elecsys, and Cobas were +49%, +29%–31%, and +22%, respectively. Discussion: Despite all investigated assays being WHO-calibrated, the Elecsys and Cobas tPSA assays produced considerably higher results than the Access and Centaur assays. Differences in fPSA-recovery between all investigated assays were even more pronounced. When applying the tPSA cutoff of 3.1 μg/L recommended for WHO-calibrated assays, the use of higher calibrated assays may lead to unnecessary prostate biopsies. Conversely, if the historical threshold of 4 μg/L is applied when using WHO-calibrated assays, it could lead to falsely omitted prostate biopsies.

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Role of a novel race-related tumor suppressor microRNA located in frequently deleted chromosomal locus 8p21 in prostate cancer progression

Carcinogenesis ◽

10.1093/carcin/bgz058 ◽

2019 ◽

Vol 40 (5) ◽

pp. 633-642 ◽

Cited By ~ 3

Author(s):

Divya Bhagirath ◽

Thao Ly Yang ◽

Z Laura Tabatabai ◽

Varahram Shahryari ◽

Shahana Majid ◽

...

Keyword(s):

Prostate Cancer ◽

Tumor Suppressor ◽

Cell Lines ◽

Cancer Progression ◽

Specific Antigen ◽

Tumor Grade ◽

Clinical Samples ◽

Mesenchymal Transition ◽

Microrna Genes

Abstract The prostate cancer (PCa) genome is characterized by deletions of chromosome 8p21–22 region that increase significantly with tumor grade and are associated with poor prognosis. We proposed and validated a novel, paradigm-shifting hypothesis that this region is associated with a set of microRNA genes—miR-3622, miR-3622b, miR-383—that are lost in PCa and play important mechanistic roles in PCa progression and metastasis. Extending our hypothesis, in this study, we evaluated the role of a microRNA gene located in chromosome 8p—miR-4288—by employing clinical samples and cell lines. Our data suggests that (i) miR-4288 is widely downregulated in primary prostate tumors and cell lines; (ii) miR-4288 expression is lost in metastatic castration-resistant PCa; (ii) miR-4288 downregulation is race-related PCa alteration that is prevalent in Caucasian patients and not in African Americans; (iii) in Caucasians, miR-4288 was found to be associated with increasing tumor grade and high serum prostate-specific antigen, suggesting that miR-4288 downregulation/loss may be associated with tumor progression specifically in Caucasians; (iv) miR-4288 possess significant potential as a molecular biomarker to predict aggressiveness/metastasis; and (v) miR-4288 is anti-proliferative, is anti-invasive and inhibits epithelial-to-mesenchymal transition; and (vi) miR-4288 directly represses expression of metastasis/invasion-associated genes MMP16 and ROCK1. Thus, the present study demonstrates a tumor suppressor role for a novel miRNA located with a frequently lost region in PCa, strengthening our hypothesis that this locus is causally related to PCa disease progression via loss of microRNA genes. Our study suggests that miR-4288 may be a novel biomarker and therapeutic target, particularly in Caucasians.

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Immunohistochemical characterization of a 183 KD myeloid-specific-DNA- binding protein in B5 fixed, paraffin-embedded tissues, and bone marrow aspirates by monoclonal antibody BM-1

Blood ◽

10.1182/blood.v70.4.1124.bloodjournal7041124 ◽

1987 ◽

Vol 70 (4) ◽

pp. 1124-1130

Author(s):

AL Epstein ◽

M Samoszuk ◽

E Stathopoulos ◽

GS Naeve ◽

CV Clevenger ◽

...

Keyword(s):

Monoclonal Antibody ◽

Bone Marrow ◽

Dna Binding ◽

Cell Lines ◽

Solid Phase ◽

Specific Antigen ◽

Precursor Cells ◽

Myelogenous Leukemia ◽

Nuclear Antigen ◽

Cortex Of The Thymus

A monoclonal antibody, designated BM-1, which is reactive in B5 formalin-fixed, paraffin-embedded tissues, has been generated against a cytoplasmic and nuclear antigen expressed in human myeloid precursor cells and derived leukemias. Using the avidin-biotin-complex immunoperoxidase procedure, BM-1 was found to stain selectively myeloid precursor cells in normal bone marrow and mature granulocytes in the blood. In a screen of 26 normal adult and fetal human organs fixed in B5 formalin, BM-1 was negative in all nonhematopoietic tissues with the exception of tissue granulocytes and scattered cells in the peripheral cortex of the thymus. Likewise a screen of 30 solid tumor cell lines including a spectrum of carcinomas, sarcomas, and neural-derived tumors was negative. BM-1 was also negative with 21 T and B cell lymphomas and 11 Hodgkin's disease tumors. A preliminary study of tumors of the hematopoietic system revealed that BM-1 was reactive with M2 and M3 acute myelogenous leukemias (AML), chronic myelogenous leukemias (CML) and myelomonocytic leukemias, and granulocytic sarcomas. M1, M4, M5, and M6 AML clot preparations were negative in this study, indicating that BM-1 may have a role in the histopathologic diagnosis of myelogenous leukemia. Myeloid leukemic cell lines HL-60, ML-2, KG1, and TPH-1-O showed BM-1 nuclear and/or cytoplasmic reactivity in a subpopulation of cells, but erythroid and lymphoid leukemias and all lymphoma cell lines were negative. Immunoperoxidase studies of a panel of fetal tissues showed BM-1 positive cells in the peripheral cortex of the thymus and portal myelopoietic regions of the liver at 18 weeks gestation. Finally, DNA-cellulose and solid phase radioimmunoassay (RIA) techniques developed in our laboratory demonstrate that the BM-1 antigenic domain is reactive only after binding to eukaryotic but not prokaryotic single- or double-stranded DNA. Immunoblot techniques using a DNA-cellulose purified protein sample revealed that BM-1 recognizes a 183 kD protein. These studies indicate that BM-1 is recognizing a myeloid-specific antigen that, because of its DNA binding characteristics, may have an important role in the differentiation of myeloid cells at the molecular level.

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Abbott IMX Evaluated for Assay of Prostate-Specific Antigen in Serum

Clinical Chemistry ◽

10.1093/clinchem/38.10.2140 ◽

1992 ◽

Vol 38 (10) ◽

pp. 2140-2142 ◽

Cited By ~ 24

Author(s):

A M Dnistrian ◽

M K Schwartz ◽

C A Smith ◽

J S Nisselbaum ◽

W R Fair

Keyword(s):

Prostate Cancer ◽

Prostate Specific Antigen ◽

Quantitative Measurement ◽

Solid Phase ◽

Specific Antigen ◽

Analytical Sensitivity ◽

Standard Curve ◽

Coefficients Of Variation ◽

Microparticle Enzyme Immunoassay ◽

Automated Immunoassay

Abstract We evaluated a new fully automated procedure for quantitative measurement of prostate-specific antigen (PSA) by the Microparticle Enzyme Immunoassay (MEIA) technology developed for the Abbott IMx automated immunoassay system. The performance characteristics of the Abbott IMx PSA assay (y) were evaluated and compared with those of the Hybritech Tandem-E PSA assay (x), a solid-phase two-site immunoenzymometric assay. PSA values for both assays were well correlated (r = 0.99); regression analysis yielded the equation y = 0.92x - 0.23 micrograms/L. The Abbott assay proved reliable and reproducible, as shown by the intra- and interassay coefficients of variation (2.0-3.4% and 3.1-4.7%, respectively). The assay gave a linear standard curve up to 100 micrograms/L and was very sensitive (detected PSA < 0.1 microgram/L). This analytical sensitivity was comparable with that of the Tandem-E PSA assay. Overall, the IMx PSA assay demonstrated the accuracy, precision, linearity, and intermethod correlation required for monitoring patients with prostate cancer.

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Importance of repeat laterally directed sextant prostate biopsy for detection of prostate cancer in high-risk patients

Medicina ◽

10.3390/medicina43110108 ◽

2007 ◽

Vol 43 (11) ◽

pp. 843

Author(s):

Kęstutis Vaičiūnas ◽

Stasys Auškalnis ◽

Aivaras Matjošaitis ◽

Antanas Mickevičius ◽

Ramūnas Mickevičius ◽

...

Keyword(s):

Prostate Cancer ◽

High Risk ◽

Prostate Biopsy ◽

Specific Antigen ◽

Antigen Level ◽

Ultrasound Guided ◽

High Risk Patients ◽

Prostate Biopsies ◽

Risk Patients ◽

Detect Prostate Cancer

Our purpose was to evaluate the relevance of repeat laterally directed sextant prostate biopsy for detection of prostate cancer in high-risk patients. Material and methods. Our study included 195 men at high risk for prostate cancer (elevated prostatespecific antigen level and/or abnormal prostate detected by digital rectal examination). We consulted the patients in outpatient department of Kaunas University of Medicine Hospital during 2003–2007. We performed transrectal ultrasound-guided laterally directed sextant prostate biopsy in every patient. For the patients with benign histological findings and increased risk of prostate cancer, laterally directed sextant biopsies were repeated. Results. Prostate cancer was detected in 30.3% of patients (59/195) on the first prostate biopsy, in 13.1% (11/84) on the second prostate biopsy, in 10.3% (4/39) on the third, and in 7.7% (1/13) on the forth biopsy. After all biopsies, prostate cancer was detected in 38.5% (75/195) of patients, and it differed significantly from the percentage of prostate cancer cases detected on the first biopsy (30.3%, P=0.04). We detected 78.7% (59/75) of all prostate cancer cases by the first laterally directed sextant prostate biopsy. The rest 21.3% (16/75) of cases we detected by repeat biopsies. The second laterally directed sextant prostate biopsy revealed additional 14.6% (n=11) of prostate cancer cases and increased the detection of prostate cancer to 93.3% (70/75). At the time of the first prostate biopsy, prostate cancer was diagnosed most frequently when patients had both risk factors: elevated prostate-specific antigen level and abnormal digital prostate examination; prostate cancer was diagnosed in 45.3% of these patients. The odds ratio to detect prostate cancer by the first biopsy in patients with elevated prostate-specific antigen level and abnormal digital prostate examination was 3.7, and odds ratio to detect prostate cancer by repeat biopsies was 4.7. Conclusions. Repeat ultrasound-guided laterally directed sextant prostate biopsies reveal more cases of prostate cancer as compared to the first prostate biopsy. The majority of prostate cancer cases (93.3%) are detected by the first and second laterally directed sextant prostate biopsies. After the first negative prostate biopsy, we recommend to repeat prostate biopsy in high-risk patients.

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