A disposable multianalyte electrochemical immunosensor array for automated simultaneous determination of tumor markers

BACKGROUND: Automated and convenient multianalyte detection with high throughput is increasingly needed in clinical diagnosis. We developed a disposable 4-by-2 array for programmed simultaneous amperometric immunoassay of 4 tumor markers. METHODS: We used a screen-printed technique, 1-step immobilization method, and flow injection technique. We immobilized carcinoembryonic antigen, alpha-fetoprotein, beta-human choriogonadotropin, and carcinoma antigen 125 as model analytes in a redox mediator-grafted, biopolymer-modified, screen-printed carbon electrode array to capture corresponding horseradish peroxidase-labeled antibodies in competitive immunoreactions. The simultaneous multianalyte immunoassay was automatically carried out to amperometrically monitor the mediator-catalyzed enzymatic response to hydrogen peroxide, which decreased in proportion to the concentrations of analytes in samples. RESULTS: The multianalyte immunosensor array had a throughput of 60 samples/h and allowed simultaneous detection of carcinoembryonic antigen, alpha-fetoprotein, beta-human choriogonadotropin, and carcinoma antigen 125 in clinical serum samples with concentrations up to 188 microg/L, 250 microg/L, 266 IU/L, and 334 kIU/L, respectively. The detection limits (limits of the blank, mean of blank plus 3 SD) were 1.1 micro/L, 1.7 microg/L, 1.2 IU/L, and 1.7 kIU/L. The inter- and intraassay imprecision (CVs) of the immunosensor arrays were <7.8% and <9.0%, respectively. The immunosensor arrays were stable for 28 days. CONCLUSIONS: This newly constructed immunosensor array provides a simple, automated, simultaneous multianalyte immunoassay with high throughput, short analytical time, and sufficiently low detection limits for clinical application. This method offers the capability of miniaturizing the multianalyte detection device.     

Benign prostate-specific antigen (BPSA) in serum is increased in benign prostate disease

BACKGROUND: BPSA is a "benign" form of free prostate-specific antigen (PSA) that is increased in prostate transition zone tissues of men with pathologic benign prostatic hyperplasia (BPH). We developed an immunoassay to determine the concentration of BPSA in the serum of men with BPH. METHODS: The BPSA antigen was purified by HPLC, and murine monoclonal antibodies were prepared by standard methods. A fluorogenic ELISA was developed with high specificity for BPSA and no cross-reactivity with other forms of PSA. RESULTS: The BPSA immunoassay had a lower limit of detection of 6 ng/L and a cross-reactivity of <1% with all other clipped and nonclipped forms of PSA. The BPSA antibody was specific for the internal Lys(182) cleavage site that characterizes BPSA. Biopsy-negative men with a median total PSA of 4.8 micro g/L had a median of 0.22 micro g/L BPSA, representing 25% of the free PSA in serum. BPSA ranged from 0% to 60% of the free PSA in serum. BPSA in a cohort of cancer serum also comprised 25% of the free PSA. Control serum from women or men without increased PSA had nondetectable BPSA. CONCLUSIONS: BPSA is a significant percentage of the free PSA in BPH serum but not in control serum. The presence of prostate cancer does not alter the relative proportions of BPSA in sera with <10 micro g/L PSA. BPSA has a wide distribution of concentrations in the serum and may provide clinical information for the study of men with BPH.     

A novel, label-free immunosensor for the detection of α-fetoprotein using functionalised gold nanoparticles

Background and objectives

Novel immunoassay methods based on electrochemical sensors have been developed, but most of these immunosensors are unsuitable for clinical detection because their preparation requires complicated chemical procedures and because their detection sensitivity is restricted. In order to develop a highly sensitive, label-free amperometric sensor for immunoassays, we synthesised novel, functionalised gold nanoparticles (SV-GNP) by covalently capping the surface of gold nanoparticles (GNP) with 1,1′-bis-(2-mercapto)-4,4′-bipyridinium dibromide, a kind of sulfhyrdryl viologen (SV).

Design and methods

We fabricated an immunosensor in a multi-step fashion, by first coating the SV-GNP onto a glassy carbon electrode surface; the resulting electrode core could then adsorb a suitable antibody in a second step to afford the desired immunosensor. α-fetoprotein (AFP) was used as a model analyte in this work.

Results

The anti-AFP/SV-GNP-modified electrode was sensitive to AFP with a linear relationship between 1.25 and 200 ng/mL and a correlation coefficient of 0.9983; the detection limit at a signal to noise ratio of 3 was 0.23 ng/mL under optimal conditions. In addition, the proposed immunosensor exhibited good sensitivity, selectivity, stability and long-term maintenance of bioactivity.

Conclusion

The described immunosensor preparation and immunoassay methods offer promise for label-free, simple, and cost-effective analysis of biological samples.     

PSA-based parameters

Serum prostate-specific antigen (PSA) is used for the screening and early detection of prostate cancer. We are, however, confronted with the dilemma that a significant number of unnecessary biopsies are unavoidable especially in the serum PSA range of 4 to 10ng/ ml. It has been reported that age-specific PSA reference ranges, PSA velocity, PSA molecular forms and volume-adjusted PSA are valuable tools to improve specificity for early diagnosis of prostate cancer. In recent years, free PSA has been demonstrated to be composed of several isoforms including pPSA, BPSA and so on. Clinical values of these new PSA isoforms as well as human glandular kallikrein 2 are anticipated to be fully investigated to reduce unnecessary biopsies without missing a significant number of prostate cancer in the near future.     

Electrochemical detection of hepatitis B surface antigen using colloidal gold nanoparticles modified by a sol-gel network interface

BACKGROUND: A novel potentiometric immunosensor for the detection of hepatitis B surface antigen has been developed by self-assembling gold nanoparticles to a thiol-containing sol-gel network. METHODS: A cleaned gold electrode was first immersed in a hydrolyzed (3-mercaptopropyl) trimethoxysilane sol-gel solution to assemble a three-dimensional silica gel, and then gold nanoparticles were absorbed onto the thiol groups of the sol-gel network. Finally, hepatitis B surface antibody was assembled onto the surface of the gold nanoparticles. The self-assembling procedure was characterized by cyclic voltammetry and electrochemical impedance spectroscopy. Detection is based on the change in potentiometric response before and after the antigen-antibody reaction. RESULTS: Tests relating to the detection of hepatitis B surface antigen demonstrate that the potentiometric immunosensor exhibited a rapid potentiometric response (<4 min), with high sensitivity, good reproducibility, and long-term stability. The linear range was from 4 to 960 ng.mL(-1) with a detection limit of 1.9 ng.mL(-1) (S/N = 3) and the lifetime was 1 month. CONCLUSION: Analytical results of several specimens using the developed technique showed satisfactory agreement with those from an ELISA method. This method shows promise for detecting HBsAg in clinical specimens.     

Prostate-specific antigen and prostate volume: A meta-analysis of prostate cancer screening criteria

Objective: To establish the value of serum prostate-specific antigen (PSA) and prostatespecific antigen per unit volume of prostate gland (PSAD) in detecting prostate carcinoma (CaP) in a hypothetical screening algorithm, a meta-analysis of the sensitivities, specificities, predictive values and likelihood ratios were combined from the published data. Data Sources: Journal articles identified by a MEDLINE database search from 1988 to October 1992, using prostate-specific antigen as a key word were used to calculate the distribution of PSA in healthy men, men with benign prostatic hyperplasia (BPH) and men with prostate carcinoma (CaP) Study Selection: Only studies that contained the specified serum PSA values and patient outcomes were included. Data Extraction: The distributions of the serum PSA were plotted versus serum PSA for healthy men (2567), men with BPH (798) and men with CaP (835) from the abstracted data. Prostate volume distributions were estimated from the published transrectal ultrasound (TRUS) calculations. Data Synthesis: Hypothetical cohorts of 1,000 men between the ages of 60 and 70 years were screened using three different screening decision algorithms. Using a serum PSA cutoff of 3.0 ng/ml for referral for transrectal biopsy, 59 of 80 (74%) CaP would be detected and 21 (26%) would be missed. 209 transrectal biopsies would be performed, and 150 (72%) of them would be negative for CaP. Using a serum PSA cutoff of 4.0 ng/ml, 52 of 80 (65%) CaP would be detected and 28 (35%) would be missed. 146 transrectal biopsies would be performed, and 94 (64%) of them would be unnecessary. Using a cutoff of 2.0 ng/ml for serum PSA and 0.1 ng/ml/cc for PSAD, 55 of 80 (69%) of the cancers would be detected and 25 (31%) would be missed. Only 84 transrectal biopsies would be performed, and 29 (35%) of them would be negative for cancer. Conclusion: This algorithm maximizes the number of cancers detected (true-positive cases) and at the same time reduces the number of false-positive cases, minimizing the number of patients who would have to receive an unnecessary transrectal biopsy, compared to using a serum PSA cutoff of 3.0 or 4.0 ng/ml. © 1993 Wiley-Liss, Inc.     

Management of prostate-specific antigen relapse in prostate cancer: a European Consensus

A European Consensus on the management of prostate-specific antigen (PSA) relapse in patients with prostate cancer has been formulated. The key recommendations proposed are that total PSA is the best detection tool for prostate cancer, with free and complexed PSA having a role in the PSA range 1-4 ng/ml. PSA relapse after radical prostatectomy (RP) has been defined as a value of 0.2 ng/ml with one subsequent rise, while the ASTRO definition should be used after radiotherapy. A PSA level of less than 0.4 ng/ml after hormonal therapy can be considered an indicator of a positive response. Continuous assessment using nomograms or artificial neural networks will help to determine whether progression after local therapy is distant or local, which is the basis for treatment decisions. Secondary treatment after local failure of RP should be initiated when PSA levels reach 1.0-1.5 ng/ml and salvage radiotherapy can be considered with or without hormonal therapy. Local failure after radiotherapy can be treated with a choice of high-intensity-focused ultrasound, salvage RP (only in highly selected patients), cryotherapy or external beam radiation. Treatment of distant failure involves hormonal manipulation, the type and the timing of which is based on both physician and patient preferences.     

Elimination of serum complexed prostate-specific antigen after radical retropubic prostatectomy.

Total prostate-specific antigen (PSA) and complexed PSA were determined in venous blood from 12 patients with prostate cancer before and after radical prostatectomy by using Immuno 1 PSA assays. The elimination kinetics of complexed PSA were compared with that of total PSA. Nearly constant concentrations of complexed PSA were found during the first six hours after surgery, in contrast to the rapid elimination of free PSA and the significant decrease of total PSA. From day one to ten there was a continuous and nearly identical decrease of complexed PSA compared to total PSA. Our findings suggest that the initial rapid decrease of free PSA immediately after operation could be caused by formation of new PSA-complex.     

Supersensitive time-resolved immunofluorometric assay of free prostate-specific antigen with nanoparticle label technology.

BACKGROUND: The extreme specific activity of the long-lifetime fluorescent europium(III) chelate nanoparticles and the enhanced monovalent binding affinity of multivalent nanoparticle-antibody bioconjugates are attractive for noncompetitive immunoassay. METHODS: We used a noncompetitive, two-step immunoassay design to measure free prostate-specific antigen (PSA). Europium(III) chelate nanoparticles (107 nm in diameter) were coated with a monoclonal anti-PSA antibody (intrinsic affinity, 6 x 10(9) L/mol). The nanoparticle-antibody bioconjugates had an average of 214 active binding sites per particle and a monovalent binding affinity of 7 x 10(10) L/mol. The assay was performed in a low-fluorescence microtitration well passively coated with an another monoclonal anti-PSA antibody (affinity, 2 x 10(10) L/mol), and the europium(III) fluorescence was measured directly from the bottom of the well by a standard time-resolved microtitration plate fluorometer. RESULTS: The detection limit (mean + 2 SD) was 0.040 ng/L (7.3 x 10(5) molecules/mL), and the dynamic detection range covered four orders of magnitude in a 3-h total assay time. The imprecision (CV) over the whole assay range was 2-10%. The detection limit of the assay was limited by the fractional nonspecific binding of the bioconjugate to the solid phase (0.05%), which was higher than the nonspecific binding of the original antibody (<0.01%). CONCLUSIONS: The sensitivity of the new assay is equal to that of the ambient-analyte, microspot immunoassay and will be improved by use of optimized, high binding-site density nanoparticle-antibody bioconjugates with reduced nonspecific binding and improved monovalent binding affinity.     

Sensitive and specific immunodetection of human glandular kallikrein 2 in serum

BACKGROUND: Human glandular kallikrein 2 (hK2) is expressed in the prostate and is present in serum from men with prostate cancer. Specific detection in serum is difficult mainly because of low concentrations and immunological cross-reactivity with prostate-specific antigen (PSA). Our objectives were to design an assay with improved analytical detection and functional sensitivity and nonsignificant cross-reactivity with PSA, and to characterize different immunoreactive forms of hK2. METHODS: In the assay, critical PSA epitopes were blocked with four monoclonal antibodies (MAbs) specific for PSA. Subsequently, hK2 was captured using a MAb against hK2 (5% cross-reactivity with PSA), and after washing, hK2 was detected by a europium-labeled MAb with identical affinity for hK2 and PSA. RESULTS: The analytical detection limit was <10 ng/L, and functional sensitivity was 30 ng/L. Cross-reaction with PSA was <0.01%. Between-assay imprecision was 3.1% for 1600 ng/L hK2 and 4. 8% for 160 ng/L hK2; corresponding values for within-assay precision were 1.9% and 4.5%, respectively. Complexes of hK2-alpha(1)-antichymotrypsin (ACT) were detected in vitro with -6% bias compared with the free form of hK2. Gel filtration of patient samples showed that hK2 correlated in size mainly with free hK2; only 4-19% corresponded to hK2 possibly complexed with ACT or protein C inhibitor. CONCLUSIONS: Our assay had extremely low cross-reactivity with PSA, provided a very low detection limit, and allowed close to equimolar detection of the free and complexed forms of hK2. Moreover, we found that free hK2 is the predominant immunoreactive form of hK2 in serum.     

Enhancing a clenbuterol immunosensor based on poly(3,4-ethylenedioxythiophene)/multi-walled carbon nanotube performance using response surface methodology

Clenbuterol (CLB) is an illegal antibiotic for livestock, which is misused as a growth promoter drug. In this study, an immunosensor modified with poly(3,4-ethylenedioxythiophene) (PEDOT), multi-walled carbon nanotubes (MWCNT) and anti-clenbuterol antibody (Ab) was developed for the detection of CLB. A screen-printed carbon electrode (SPCE) was modified with PEDOT/MWCNT as a sensor platform before immobilizing Ab for specific CLB binding through a competitive-type immunoassay. Free CLB in the sample solution competed with clenbuterol-horseradish peroxide (CLB–HRP) to bind with Ab. A high current signal was obtained after optimization of the electrochemical immunoassay conditions (pH, incubation temperature, antigen (Ag) incubation time and % blocking) using the response surface methodology/central composite design (RSM/CCD). The developed immunosensor is highly reproducible and sensitive with good storage stability, which are necessary for practical application. In real sample application, this immunosensor produces comparable results with liquid chromatography-mass spectrometry; thus, it is useful for CLB screening and monitoring in real meat samples.

A clenbuterol immunosensor was developed with a poly(3,4-ethylenedioxythiophene)/multi-walled carbon nanotube-modified screen-printed carbon electrode and optimized using response surface methodology.     

Prostate-specific antigen and prostate gland volume: correlation and clinical application.

We studied 103 patients seen in our Prostate Cancer Detection Clinic to determine whether a correlation exists between serum prostate-specific antigen (PSA) values and ultrasound-calculated prostate gland volume. Seventy men (68%) had a PSA value less than or equal to 4 ng/ml (our upper limit of normal). The men were subclassified by prostate gland volume at arbitrary break points. Twenty-five men (24%) had a prostate gland volume less than or equal to 25 cm3; in 96%, the PSA value was less than or equal to 4 mg/ml. Further analysis revealed that the percentage of men with a normal serum PSA value decreased as the prostate gland volume increased; 65.6% of the group with a gland volume between 25 and 50 cm3 (40 of 61) and 35.5% of the group whose prostate volume exceeded 50 cm3 (6 of 17) had PSA values less than or equal to 4 ng/ml. Four men had PSA values greater than 20 ng/ml; all had prostate cancer. Cancer was diagnosed in four additional patients, three with PSA values between 5 and 10 ng/ml and one with a PSA value less than 4 ng/ml. There appears to be a direct relationship between prostate gland volume and PSA value, as well as a cancer value threshold. The clinical implications of these findings are discussed.     

Levels of free prostate-specific antigen (PSA) can be selectively measured by heat treatment of serum: free/total-PSA ratios improve detection of prostate carcinoma

We studied a simple heat treatment method for measuring free prostate-specific antigen (PSA). Samples were incubated at 56, 58, and 60°C for 5, 15, 30, 45, and 60 min. Then, 1 ml samples were fractionated on a Sephacryl S-200 gel filtration column to separate 1-antichymotrypsin-complexed PSA (ACT-PSA) and free PSA. Values of ACT-PSA decreased with increasing incubation temperature and time, whereas free-PSA remained relatively constant. The optimal temperature and time for incubation were 58°C and 30 min. Using free/total-PSA ratios, we were able to distinguish between benign prostatic hyperplasia and prostate carcinoma in patients whose PSA was in the diagnostic ‘grey zone', i.e. 4.1 to 10.0 ng/ml. Through receiver operating characteristic curve analysis, the area under the curve increased from 0.675 to 0.871 when comparing the performance of total PSA to the free/total-PSA ratio. Thus, clinical application of our present methodology may reduce the need to obtain prostatic biopsies in patients whose PSA level is within the diagnostic ‘grey zone'.     

Noncompetitive enzyme immunoassay for carcinoembryonic antigen by flow injection chemiluminescence

BACKGROUND: Recently, many automated immunoassay analyzers have been developed for carcinoembryonic antigen (CEA) to overcome the shortcomings in traditional immunoassay methods that are time-consuming and labor-intensive. Flow injection immunoassay (FIIA) has been increasingly applied to laboratory medicine due to its ease in automation, rapid speed and reproducible results. It is important to develop a FIIA method for CEA determination. METHODS: Based on a noncompetitive immunoassay format, a CEA-immobilized immunoaffinity column inserted in the flow system was used to trap the unbound horseradish peroxidase (HRP)-labeled antibody after an off-line incubation of CEA and HRP-labeled anti-CEA. The trapped enzyme conjugate was detected by injecting substrates to produce an enhanced chemiluminescence (CL). RESULTS: The linear range for CEA was 1.0-25 ng/ml with a correlation coefficient of 0.997 and a detection limit of 0.5 ng/ml. The sampling and chemiluminescence detection time for one sample was 5 min after a preincubation procedure of 25 min. Twenty five human serum samples detected by this method were in good agreement with the results obtained by immunoradiometric assay (IRMA). CONCLUSIONS: This method could be used for rapid analysis of CEA and potentially other antigens.     

Specificity and accuracy of TRUS-measured PSA-density and transition zone-PSA in the diagnosis of prostate cancer

Between 4 and 15 ng/ml serum prostate-specific antigen (PSA) has a low specificity for prostate cancer (PCa). One accepted method to enhance this specificity is transrectal ultrasonography (TRUS)-measured PSA-density (PSA-D). We compared this method with a new alternative, transition zone PSA (PSA-TZ). We measured total and transition zone prostatic volumes by TRUS and calculated PSA-D and PSA-TZ in 59 patients with suspicion of PCa and PSA between 4 and 15 ng/ml. All patients then had sextant biopsies of the prostate, 30 were positive for PCa and 29 showed benign tissue. With a cut-off value of 0.35, PSA-TZ had a positive predicted value of 77% for PCa, whereas PSA-D, with a cut-off value of 0.12, had a positive predicted value of 55%. Our data suggest PSA-TZ to be more reliable for avoiding unnecessary biopsies in patients with PCa suspicion and serum PSA below 15 ng/ml. PSA-TZ, calculated by TRUS, enhances the specificity of PSA for needle biopsy diagnosis of PCa.     

Correlations among prostatic biopsy results, transrectal ultrasound findings and PSA levels in diagnosing prostate adenocarcinoma.

OBJECTIVE: The objective of this study was to evaluate transrectal ultrasound (TRUS) findings and prostate-specific antigen (PSA) levels in relation to prostatic biopsy results and to analyze their individual and combined performances in diagnosing prostate adenocarcinoma (PAC). METHODS: Men (n=143) with PSA levels above 4 ng/ml underwent TRUS and randomized ultrasound-guided prostatic biopsy through the peripheral zone, including additional hypoechoic nodules biopsies, if they were noted on TRUS. Data related to TRUS, biopsy, and PSA level results were then correlated. RESULTS: A significant correlation between TRUS images suspicious for PAC and a biopsy-confirmed diagnosis of PAC, or between the lack of such images and a negative biopsy result, was not found. However, a significant correlation was found between positive biopsy results and PSA levels greater or equal to 10 ng/ml. The sensitivity of transrectal ultrasound in making a diagnosis of PAC was 63%, whereas its specificity was 73%. CONCLUSION: We conclude that while the separate performances of these examinations were not effective in diagnosing PAC, the integrated use of these methods was more adequate for making the diagnosis.     

PSA、PSAD、f／tPSA在早期前列腺癌诊断作用的研究

目的探讨前列腺特异性抗原（PSA）、PSA密度（VSXO）、游离PSA／总PSA比值（f／tPSA）在诊断早期前列腺癌（PCa）中的价值。方法对640例患者行前列腺穿刺活检,其中PSA〈4．0ng／ml者36例为直肠指诊及直肠超声可疑者。病理诊断为415例良性前列腺增生和225例前列腺癌,利用酶联免疫法（ELISA）测定患者血清中的PSA、游离PSA（fPSA）,利用经直肠超声测定前列腺体积,并计算出f／tPSA及PSAD进行统计学分析。结果PCa组患者血清的PSA、PSAD明显高于前列腺良性增生（BPH）组（P〈0．01）,f／tPSA明显低于BPH组（P〈0．01）,但当血清PSA为4—20ng/ml时,两组患者PSA没有明显差异（P〉0．05）。以PSA〉4．0ng／ml、PSAD〉0．15、f／tPSA〈0．18为临界值可明显提高对PCa诊断的特异性,特别是当血清PSA为4—20ng／ml时对提高临床诊断更有意义。结论联合测定PSA、fPSA并计算f／tPSA及PSAD对诊断PCa具有明显临床意义。     

Clinical efficacy of prostate cancer detection using power doppler imaging in American and Japanese men

PURPOSE: The aim of this study was to compare the detection rates of tumor vascular flow as measured by power Doppler imaging (PDI) in 2 populations and to determine whether PDI can reduce the number of unnecessary prostate biopsies in men with serum prostate-specific antigen (PSA) concentrations less than 10.1 ng/ml. METHODS: The patient populations were Japanese (group 1) and American (group 2) men with either serum PSA concentrations of 4.1-10.0 ng/ml or abnormal findings on digital rectal examination (DRE) plus PSA concentrations less than 4.1 ng/ml. We compared the overall diagnostic accuracy of DRE, gray-scale transrectal sonography (TRUS), and PDI between the 2 groups. RESULTS: In total, 275 men were studied, 154 in group 1 and 121 in group 2. Cancer was identified in 27% of men in group 1 and in 60% of group 2. Men with cancer in both groups differed significantly in age, peripheral zone volume, and mean number of positive biopsy cores. The sensitivity and specificity of PDI in group 2 were significantly inferior to those in group 1. The negative predictive value (NPV) of PDI was significantly higher for group 1 than for group 2. The NPV of PDI in group 1 was equivalent to that for the combination of DRE and TRUS, whereas the NPV for PDI in group 2 was significantly inferior to that of DRE and TRUS.CONCLUSIONS: Tumor vascularity could be detected by PDI more effectively in Japanese men with cancer than in American men with cancer. We hypothesize that this difference was a result of larger cancer volumes and smaller prostates in the Japanese men. PDI did not provide any performance advantage over DRE and TRUS in avoiding unnecessary biopsies.     

血清PSA、FPSA/TPSA、PSAD对前列腺癌诊断的临床意义

目的　进一步了解前列腺特异性抗原 (PSA)、游离PSA/总PSA(FPSA/TPSA)、PSA密度 (PSAD)对国人前列腺癌诊断的意义。方法　选择前列腺癌 40例 ,良性前列腺增生 46例 ,PSA <2 0ng/ml,比较两组间PSA、FPSA/TPSA、PSAD的差异及当取不同界值时对前列腺癌诊断的意义。结果　PSA、PSAD两组间均数差异有显著意义 (P <0 .0 1及P <0 .0 5 ) ;FPSA/TPSA两组均数差异无统计学意义 (P >0 .0 5 ) ;当PSA取 4ng/ml、6ng/ml及 10ng/ml为界值时 ,诊断前列腺癌的敏感性和特异性分别为 92 .5 %和 45 .7%、67.5 %和 78.3 %、3 0 .0 %和 91.3 % ;当PSAD分别以 0 .15和 0 .2为界值时 ,诊断前列腺癌的敏感性和特异性分别为 5 0 %和 67.4%、3 0 %和 84.8%。结论　当PSA≥ 10ng/ml时 ,提示高度怀疑前列腺癌 ,应进行前列腺穿刺活检确诊 ;PSAD诊断前列腺癌与PSA相比较无明显优越性。