Molecular forms of prostate‐specific antigen in serum with concentrations of total prostate‐specific antigen <4 μg/L: Are they useful tools for early detection and screening of prostate cancer?

Molecular forms of prostate-specific antigen (PSA) improve the differentiation between benign prostatic hyperplasia (BPH) and prostate cancer (PCa) in men with total PSA concentrations between 4 and 10 microg/l. To evaluate the diagnostic utility of free PSA (fPSA) and complexed PSA forms for identification of men with PCa in the low PSA range of <4 microg/l, total PSA (tPSA), alpha(1)-antichymotrypsin complexed PSA (PSA-ACT) and fPSA (Roche Elecsys [ES] system) as well as tPSA and complexed PSA (cPSA) (Bayer Immuno 1 system) were measured in archival serum samples from 31 untreated patients with PCa, 66 patients with BPH, and 90 men without prostatic disease. The median ratios of fPSA/tPSA, PSA-ACT/tPSA and cPSA/tPSA were significantly different between patients with BPH and PCa (27.2 vs. 19.4%, 64 vs. 88%, 77.2 vs. 88.2%, p < 0.05). No associations between PSA forms and tumor stage and grade were found. Analysis of the receiver operating characteristic curves showed that these ratios could discriminate better between BPH and PCa patients than determination of the analytes tPSA, fPSA, cPSA and PSA-ACT alone. The use of one of the ratios would have eliminated roughly half of the unnecessary biopsies in this study. The ratios should be considered as potential tools to increase the selectivity of PCa detection at low PSA concentration. The ratios fPSA/tPSA and cPSA/tPSA can be determined using commercially available assays so that one of these ratios could be preferred instead of PSA-ACT determination. The ratios could be useful in assessing the risk of PCa in the individual and therefore in deciding on prostate biopsy for final diagnosis.     

Prostate specific antigen complexed to alpha-1-antichymotrypsin in patients with intermediate prostate specific antigen levels

BACKGROUND: The authors attempted to evaluate prospectively the usefulness of serum prostate specific antigen (PSA) complexed to alpha-1-antichymotrypsin (PSA-ACT) in the early detection of prostate carcinoma and its ability to discriminate between prostate carcinoma and benign prostatic hyperplasia (BPH), especially among patients with intermediate PSA levels. METHODS: Between December 1999 and August 2000, systematic sextant biopsies were performed on 281 prospective patients with prostate carcinoma who had serum PSA levels between 4.1 ng/mL and 20.0 ng/mL. The serum samples were assayed by using kits that were designed specifically for measuring serum PSA, PSA-ACT, and free PSA levels. The clinical values of PSA, PSA-ACT, the free PSA to total PSA ratio (F/T ratio), the free PSA to PSA-ACT ratio, PSA density (PSAD), and PSA-ACT density (ACTD) were compared by using receiver operating characteristic (ROC) curve analysis. RESULTS: Biopsy yielded no evidence of malignancy in 198 patients, and prostate carcinoma was confirmed in 83 patients. ROC analysis demonstrated that the area under the curve (AUC) for PSA-ACT was greater than that for total PSA and was equivalent to that for the F/T ratio in both groups of patients (PSA ranges of 4.1-20.0 ng/mL and 4.1-10.0 ng/mL, respectively). The AUC for the ACTD was greater than the AUC for the PSAD and had the highest value of all parameters. CONCLUSIONS: The measurement of PSA-ACT represents an alternative to the use of total and free PSA. The ACTD value is the most useful for discriminating between BPH and prostate carcinoma.     

PSA,PSAD,fPSA在前列腺癌诊断中的应用

目的：测定１６例前列腺癌（ＰＣａ）和３３例前列腺增生（ＢＰＨ）患者血清前列腺特异性抗原（ＰＳＡ）,前列腺特异抗原密度（ＰＳＡＤ）及游离前列腺特异抗原（ｆＰＳＡ）。方法：采用放射免疫法。结果：显示ＰＳＡＤ对ＰＣａ诊断敏感度高而特异阳性预测值低,而ＰＳＡＤ及ｆＰＳＡ／ｔＰＳＡ比值（即参数百分率）是提高ＰＣａ和ＢＰＨ鉴别诊断阳性率的一种较好指标。结论：本实验结果在实际临床应用中有重要意义。     

Prostate-specific antigen

Prostate specific antigen (PSA) is serine protease produced at high concentrations by normal and malignant prostatic epithelium. It is mainly secreted into seminal fluid, where it digests the gel forming after ejaculation. Only minor amounts of PSA leak out into circulation from the normal prostate, but the release of PSA is increased in prostatic disease. Thus PSA is a sensitive serum marker for prostate cancer but its specificity is limited by a high frequency of falsely elevated values in men with benign prostatic hyperplasia (BPH). Approximately two-thirds of all elevated values (>4 microg/l) in men over 50 years of age are due to BPH. In serum, most of the PSA immunoreactivity consists of a complex between PSA and alpha1-antichymotrypsin (PSA-ACT) whereas approximately 5-40% are free. The proportion of PSA-ACT is larger and the free fraction is smaller in prostate cancer than in benign prostatic hyperplasia (BPH). Determination of the proportion of free PSA has become widely used to improve the cancer specificity of PSA especially in men with PSA values in the 'grey zone' (4-10 microg/l). PSA also occurs in complexes with other protease inhibitors and determination of these and other markers may further improve the diagnostic accuracy for prostate cancer. Interpretation of the results for many different markers is complicated, but this can be simplified by using statistical methods. The diagnostic accuracy can be further improved by using logistic regression or neural networks to estimate the combined impact of marker results and other findings like digital rectal examination (DRE), transrectal ultrasound (TRUS) and heredity.     

Evaluation of free-to-total prostate specific antigen ratio in the diagnosis of prostate cancer

It'sreportedthatfreetototalprostatespecificantigenration(f/tPSA)canprovidemorebenefitthanthesingleuseofprostatespecificantigen(PSA)inthediagnosisofprostatecancer(PCa).WemeasuredserumPSAandfPSAlevelsin62casesofbenignprostatichyperplasia(BPH)and40casesofPCausingradioimmunoassay,withpatients'agerange59y-89y.RESULTSPSA,fPSAandf/tPSAareshowninTable1.BoththesetwogroupsshowslinearcorrelationbetweenPSAandfPSA,correlationcoefficientofBPHis0.55(P<0.01),ofPCais0.44(P<0.01).Twoslopesha…     

Significance of prostate-specific antigen--alpha(1)-antichymotrypsin complex for diagnosis and staging of prostate cancer.

OBJECTIVE: To evaluate the clinical significance of measuring the prostate-specific antigen-alpha(1)-antichymotrypsin (PSA-ACT) for differentiating prostate cancer from benign prostate hypertrophy (BPH) and for the staging of prostate cancer. METHODS: Before treatment, total PSA (tPSA) and PSA-ACT were measured in 120 patients with prostate cancer and in 150 patients with BPH using immunofluorometric techniques with different monoclonal antibodies against PSA and ACT. Furthermore, the tPSA and PSA-ACT densities of the whole prostate (PSAD and ACTD, respectively) were calculated. RESULTS: tPSA, PSAD, PSA-ACT and ACTD levels in patients with prostate cancer paralleled the clinical stage and were significantly higher than those in patients with BPH. Furthermore, these four values were significantly higher in patients with pathologically extraprostatic disease than those with organ-confined disease. Receiver operating characteristics analysis among patients with PSA values of 4.1-10 ng/ml revealed that the areas under the curve for tPSA and ACTD were similar to those for PSA-ACT and ACTD, respectively and that no significant differences in the differentiation between prostate cancer and BPH were observed among these parameters. CONCLUSIONS: Measurement of PSA-ACT provides useful information for the clinical staging of prostate cancer and differential diagnosis between prostate cancer and BPH; however, compared with tPSA, PSA-ACT may not be significantly superior in the diagnosis and staging of prostate cancer.     

游离前列腺特异性抗原与总前列腺特异性抗原比值在前列腺癌鉴别诊断中的应用

 目的 探讨游离前列腺特异性抗原（fPSA）与总前列腺特异性抗原（tPSA）比值在前列腺癌（PCa）鉴别诊断中的意义。方法 采用电化学免疫发光技术对86例前列腺良性增生（BPH）45例PCa患者和60例健康男性体检者（正常对照组）血清fPSA和tPSA同时进行测定，并计算出fPSA／tPSA，进行统计分析。结果 BPH、PCa组tPSA水平明显高于正常对照组（P＜0.05）。PCa组和BPH组的血清tPSA差异亦有统计学意义，但当tPSA在4.0 ~ 10.0 μg／L范围时，PCa组血清fPSA／tPSA比值却明显低于BPH组（P＜0.01）。把fPSA／tPSA比值划分成8个区间，当fPSA／tPSA比值15 ％作为诊断灰区PCa诊断的临界值时，诊断的敏感性、特异性、阳性预测值、阴性预测值及正确诊断指数分别为72.8 %、67.5 %、62.5 %、82.2 %、50.2 %。结论 当血清tPSA处于诊断灰区时，联合检测fPSA／tPSA比值可明显提高tPSA对PCa早期诊断的特异性。     

The clinical utility of measuring total PSA, PSA density, gamma-seminoprotein and gamma-seminoprotein/total PSA in prostate cancer prediction

BACKGROUND: To evaluate whether serum total prostate-specific antigen (PSA), PSA density (serum total PSA level divided by prostate volume), gamma-seminoprotein and gamma-seminoprotein/total PSA ratio could predict prostate cancer (PCa) prior to biopsy. METHODS: A total of 316 consecutive patients who had undergone transrectal prostate biopsy and/or transurethral resection were examined. The prostate volume was determined by transrectal ultrasonography (TRUS) and the ability of the above-mentioned four variables to distinguish PCa from benign prostatic hyperplasia (BPH) was evaluated. RESULTS: PCa was detected in 61 cases. Receiver-operating characteristic (ROC) analysis revealed that both the PSA density and serum total PSA were the most useful predictors of PCa among the four variables. For the patients with a serum total PSA level of 4.1-10.0 ng/ml, PSA density was significantly more accurate than total PSA (p < 0.005). An optimum PSA density value of 0.18 was chosen as a cutoff because it showed the highest sum of sensitivity and specificity, 92 and 54%, respectively. Using this PSA density cutoff, the number of biopsies could have been reduced to 57 from 63% when compared with a PSA density of 0.15. CONCLUSIONS: PSA density was significantly more accurate than other variables in predicting PCa. To avoid unnecessary biopsies, the PSA density cutoff value of 0.18 would be recommendable for determining a prostate biopsy for Japanese males with a serum total PSA level of 4.1-10.0 ng/ml.     

前列腺特异性抗原的检测对前列腺癌及前列腺增生的诊断意义

目的　探讨血清总前列腺特异性抗原 (t PSA)、游离PSA (f PSA)、PSA密度 (PSAD )及其f PSA/t PSA比值对前列腺癌 (PCa)及前列腺增生 (BPH )的诊断价值。方法　采用酶联免疫分析方法 (ELISA )检测未经治疗的 62例BPH患者和 2 4例PCa患者血清f PSA、t PSA水平 ,并计算f PSA/t PSA值和PSAD ,对检测结果进行统计学处理。结果　BPH组与PCa组的f PSA、t PSA水平均明显高于对照组 (P <0 .0 1) ;前列腺癌组的f PSA /t PSA值明显小于对照组及前列腺癌增生组 (P <0 .0 1) ;PCa组PSAD明显大于对照组和BPH组 (P <0 .0 1)。结论　检测f PSA/t PSA和PSAD比单一检测f PSA、t PSA可显著提高对PCa诊断的特异性及符合率 ,对前列腺体积较大的BPH和PCa患者 ,检测PSAD更有意义     

A precursor form of prostate-specific antigen is more highly elevated in prostate cancer compared with benign transition zone prostate tissue

Prostate-specific antigen (PSA) is a widely used serum marker for prostate cancer (PCa), but in the critical diagnostic range of 4-10 ng/ml it has limited specificity for distinguishing early PCa from benign prostatic hyperplasia (BPH). PSA in serum is comprised of a variety of both "free" and "complexed" forms that have been used to improve the specificity of PSA for prostate cancer detection. We previously reported that pro PSA (pPSA), the zymogen or precursor form of PSA, is a component of free PSA in the serum of PCa patients. In the current study, we examined prostate tissues to understand the origin and specificity of pPSA. PSA was immuno-affinity purified from matched sets of prostate tissues including peripheral zone cancer (PZ-C); peripheral zone noncancer; and benign tissue from the transition zone (TZ), the primary site of BPH within the prostate. We found that pPSA is differentially elevated in PZ-C, but is largely undetectable in TZ. N-terminal sequencing revealed that the pPSA was comprised primarily of [-2]pPSA and minor levels of [-4]pPSA, containing pro leader peptides of 2 and 4 amino acids, respectively. The median value of pPSA was 3% in PZ-C and 0% (undetectable) in TZ (P < 0.0026). No pPSA was detected in 13 of 18 transition zone specimens (72%), but only 2 of the 18 matched cancer specimens (11%) contained no measurable pPSA. These results demonstrate that pPSA is more highly correlated with prostate cancer than with BPH. The pPSA in serum may represent a more cancer-specific form of PSA that could help distinguish prostate cancer from BPH.     

Molecular forms of prostate-specific antigen in the serum of women with benign and malignant breast diseases.

Using a highly sensitive immunofluorometric procedure, we measured the total prostate-specific antigen (PSA) concentration in 632 sera obtained from female blood donors and women with idiopathic hirsutism, breast cancer or benign breast diseases. A total of 50 sera with total PSA > 15 ng l(-1) were fractionated by high-performance liquid chromatography (HPLC) in order to resolve the two immunoreactive molecular forms, i.e. free PSA (approximately 30 kDa) and PSA bound to alpha1-antichymotrypsin (PSA-ACT, 100 kDa). We found that breast cancer patients have presurgical serum total PSA levels similar to those of blood donors. Total serum PSA concentration decreases with age in women with idiopathic hirsutism, in cancer patients and in patients with benign breast diseases. The major molecular form of PSA in the serum of all normal and hirsute women (n = 15) is PSA bound to the proteinase inhibitor alpha1-antichymotrypsin. The major molecular form in 44% of presurgical cancer patient sera is free PSA. A total of 58% of benign breast disease patients also have in their serum mainly free PSA. We conclude that about half the patients with breast cancer or benign breast diseases have free PSA as the major molecular form in their serum, whereas patients without breast pathologies (normal blood donors, idiopathic hirsutism) have PSA bound to alpha1-antichymotrypsin as the major molecular form. The ratio of PSA/PSA-ACT may have value as a simple biochemical test for diagnosis of breast pathologies including breast cancer.     

Clinicopathological characteristics of androgen-dependent advanced prostate cancer patients with α2-macroglobulin deficiency

α2-Macroglobulin (α2M) is thought to be involved in cancer metastasis and inflammatory reaction through its functions as a proteinase inhibitor and carrier protein for interleukin-6 (IL-6). We previously reported that advanced prostate cancer (PCa) patients with multiple distant bone metastases had markedly decreased serum α2M levels (<20 mg/dl) and no detection of α2M by immunoelectrophoresis (defined as α2M deficiency). We also showed a relationship between serum α2M levels and acute inflammatory biomarkers in PCa patients with or without α2M deficiency. In this study, we analyzed in detail the clinicopathological characteristics and pathogenesis of α2M deficiency in androgen-dependent advanced PCa patients. In this study, 15 PCa patients were diagnosed at the Kitasato University Hospital. α2M levels were determined by laser-nephelometry and immunoelectrophoresis, and PSA levels were determined by enzyme immunoassay. IL-6 levels were measured by a specific luminescence sandwich-type enzyme-linked immunosorbent assay, and CRP levels were determined by latex nephelometry. Immunohistochemical staining for PSA in PCa specimens was also performed. The binding assay for purified α2M and PSA was analyzed by western blotting. α2M deficiency was specific for advanced PCa patients with multiple distant bone metastases. PSA was markedly detected in sera and prostate specimens of advanced PCa patients with α2M deficiency, and there was a negative correlation between serum α2M and PSA levels during the course of clinical treatment. Acute inflammatory biomarkers such as IL-6 and CRP were within reference range in α2M-deficient patients. The binding assay showed that PSA easily bound to α2M, which was detected as an approximately 800-kDa complex by western blotting. Further, genetic analysis of a α2M-deficient patient showed no mutations in the α2M gene. These results suggested that α2M deficiency develops from catabolism of α2M in androgen-dependent advanced PCa patients, and serum α2M level may be an indicator of PCa disease progression in addition to PSA level.     

Measurement of free PSA in the diagnosis and staging of prostate cancer

The purpose of this study was to analyze the role of total prostate-specific-antigen (PSA) and free-PSA levels in the diagnosis and clinical staging of prostate cancer. We determined total-PSA serum concentration and free-PSA percentage in 352 patients, 234 with benign prostatic hyperplasia (BPH) and 118 with prostate cancer. Clinical stage of patients with prostate cancer was T1 N0 M0 in 17, T2 N0 M0 in 27, T3-4 N0 M0 in 34 and T1-4 N0-3 M0-1 in 40. Median total-PSA serum concentration was 3.1 ng/ml in patients with BPH and 26.9 ng/ml in patients with prostate cancer, p < 0.0001. Median free-PSA level was 16.7% in patients with BPH and 8.1% in patients with prostate cancer, p < 0.0001. A cutpoint of 4.0 ng/ml detected 96.6% of the prostate cancer, but the percent rate of negative biopsies was 42.1%. For a free-PSA level of 25% in patients with total PSA greater than 4.0 ng/ml, the sensitivity was 97.4%, and the decrease in negative biopsies was 21%. Median total-PSA serum concentration in patients with prostate cancer according to clinical stage was 8.9 ng/ml for T1 N0 M0, 12.9 ng/ml for T2 N0 M0, 29.9 ng/ml for T3-4 N0 M0 and 317 ng/ml for T1-4 N1-3 M0-1, p < 0.001. Median free-PSA levels were 10.1%, 8.1%, 8.4% and 6.1% respectively, p >0.05. According to the Gleason score, median total-PSA serum concentration was 10.6 ng/ml in patients between 2 and 4, 22.3 ng/ml between 5 and 7 and 77.0 ng/ml between 8 and 10, p < 0.05. Free PSA levels were 7.7%, 8.7% and 6.6% respectively, p >0.05. Determination of percentage of free PSA appears to be a helpful method for enhancing the specificity of total PSA. A cutpoint of 25% could detect more than 95% of prostate cancers and avoid 21% of negative biopsies in patients with total PSA above 4.0 ng/ml. However, this parameter does not provide additional information about the clinical staging of prostate cancer.Int. J. Cancer 71:756-759, 1997. © 1997 Wiley-Liss Inc.     

Predictive Value of the Platelet-To-Lymphocyte Ratio in Diagnosis of Prostate Cancer

Purpose: To predict prostatic carcinoma using a logistic regression model on prebiopsy peripheral bloodsamples. Materials and Methods: Data of a total of 873 patients who consulted Urology Outpatient Clinics of FatihSultan Mehmet Training and Research Hospital between February 2008 and April 2014 scheduled for prostatebiopsy were screened retrospectively. PSA levels, prostate volumes, prebiopsy whole blood cell counts, neutrophiland platelet counts, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), biopsy resultsand Gleason scores in patients who had established diagnosis of prostate cancer (PCa) were evaluated. Results:This study was performed on a total of 873 cases, with an age range 48-76 years, divided into three groups asfor biopsy results. with diagnoses of benign prostatic hyperplasia (BPH) (n=304, 34.8 %), PCa (n=265, 30.4 %)and histological prostatitis (n=304; 34.8 %). Intra- and intergroup comparative evaluations were performed.White blood cell and neutrophil counts in the histological prostatitis group were significantly higher than thoseof the BPH and PCa groups (p=0.001; p=0.004; p<0.01). A statistically significant intergroup difference wasfound for PLR (p=0.041; p<0.05) but not lymphocyte count (p>0.05). According to pairwise comparisons, PLRwere significantly higher in the PCa group relative to BPH group (p=0.018, p<0.05, respectively). Though notstatistically significant, higher PLR in cases with PCa in comparison with the prostatitis group was remarkable(p=0.067, and p>0.05, respectively). Conclusions: Meta-analyses showed that in patients with PSA levels over4 ng/ml, positive predictive value of PSA is only 25 percent. Therefore, novel markers which can both detectclinically significant prostate cancer, and also prevent unnecessary biopsies are needed. Relevant to this issuein addition to PSA density, velocity, and PCA3, various markers have been analyzed. In the present study, PLRw ere found to be the additional predictor of prostatic carcinoma.     

A truncated precursor form of prostate-specific antigen is a more specific serum marker of prostate cancer

Prostate-specific antigen (PSA) is a widely used serum marker for prostate cancer (PCa) but has limited specificity for distinguishing early PCa from benign prostatic hyperplasia, because both PCa and benign prostatic hyperplasia release PSA into the serum. We have identified previously a truncated form of precursor PSA (pPSA) in prostate tumor extracts consisting of PSA with a serine-arginine pro leader peptide ([-2]pPSA) instead of the normally expressed 7 amino acid pro leader peptide. In the current study we developed monoclonal antibodies to detect [-2]pPSA and other isoforms of pPSA for Western blot analysis. PSA was immunoaffinity purified from 100 to 200 ml of serum from each of five men with biopsy-proven cancer and three biopsy-negative men, all with total PSA levels in the diagnostically relevant range near 10 ng/ml. The truncated [-2]pPSA was estimated to range from 25 to 95% of the free PSA in the five PCa samples but only 6-19% of the free PSA in the biopsy-negative men. Immunohistochemical studies showed positive staining for [-2]pPSA in PCa epithelium and that [-2]pPSA was enriched in cancer cell secretions. In vitro activation studies showed that human kallikrein 2 and trypsin readily activated full-length pPSA but were unable to activate [-2]pPSA to mature PSA. Thus, [-2]pPSA, once formed, is a stable but inactive isoform of PSA. Truncated [-2]pPSA may represent an important new diagnostic marker for the early detection of PCa.     

海南地区Gleason评分≥7分的前列腺癌患者血清PSA和睾酮水平与预后相关性探讨

目的:分析海南地区Gleason评分≥7分的前列腺癌（prostatic cancer,PCa）患者血清前列腺特异性抗原(prostate specific antigen,PSA)和总睾酮（total testosterone,TT）水平与5年总生存率的相关性。方法:回顾性分析2009年01月至2019年12月我院收治的前列腺癌患者106例作为PCa组,选取同期良性前列腺增生症（benign prostatic hyperplasia,BPH）患者120例作为BPH组,比较两组患者临床资料、血清PSA、TT水平;再根据PCa组患者5年生存情况分为生存组（n=81）和死亡组（n=25）,比较两组患者临床资料、Gleason评分、血清PSA、TT水平;采用多因素COX回归分析影响前列腺癌患者预后的独立危险因素;绘制受试者工作特征曲线（receiver operating characteristic curve,ROC）,分析血清PSA、TT水平早期评估前列腺癌患者预后的预测价值;采用Spearman相关性模型分析血清PSA、TT水平与病理Gleason评分的相关性。结果:PCa组患者年龄、前列腺体积、血清PSA水平高于BPH组,血清TT水平低于BPH组,差异具有统计学意义（P＜0.05）;生存组患者Gleason评分、血清PSA水平、骨转移发生率、TNM分期低于死亡组,血清TT水平高于死亡组,差异具有统计学意义（P＜0.05）;Spearman相关性分析显示,血清PSA水平与病理Gleason评分呈正相关（r=0.634,P＜0.05）,血清TT水平与病理Gleason评分呈负相关（r=-0.755,P＜0.05）;多因素COX回归分析显示,高PSA水平（HR=1.352）、高Gleason评分（HR=4.576）、高TNM分期(HR=2.937)和骨转移（HR=1.258）是前列腺癌患者预后的独立危险因素（P＜0.05）,高TT水平（HR=0.063）是前列腺癌患者预后的保护因素（P＜0.05）;ROC曲线显示,血清PSA、TT水平及两者联合早期预测前列腺癌患者预后的曲线下面积（area under curve,AUC）为0.811、0.887和0.934,敏感度为88.00%、96.00%和92.00%,特异度为68.73%、72.84%和82.72%,截点值分别为21.51 ng/mL和3.74 ng/mL。结论:前列腺癌患者血清PSA、TT水平可作为早期评估患者预后的重要指标,其与病理Gleason评分存在高度相关性。     

Factors influencing the ratio of free to total prostate-specific antigen in serum

The ratio of free prostate-specific antigen (f-PSA) to total PSA (t-PSA) in serum, calculated as percent free PSA (f-PSA%), is lower in patients with prostate carcinoma (PCa) than in patients with benign prostate hyperplasia (BPH). This parameter facilitates discrimination between the 2 groups of patients, but there is an overlapping of data. A better understanding of factors influencing this ratio is of practical importance. Therefore, f-PSA% was measured in controls and patients suffering from BPH, PCa and chronic prostatic inflammation with t-PSA concentrations up to 20 μg/l using the IMMULITE assays. The relationships of f-PSA% to clinical situation, age, prostate volume, kind of treatment, and stage and grade of tumor were calculated. Compared with controls or BPH patients, mean f-PSA% values were reduced in PCa patients and in patients with chronic prostatic inflammation. The prostate volume was the most important factor to influence f-PSA%. The difference of f-PSA% between PCa and BPH patients with prostate volumes smaller than 40 cm³ was lost if the prostate volumes exceeded 40 cm³. No relationship of f-PSA% to pTNM stage or grade of tumor was observed. In contrast to t-PSA concentrations, the f-PSA% values were not age-dependent and were not influenced by any kind of treatment in BPH and PCa patients either, which simplifies the use of f-PSA% compared with t-PSA. Thus, for using f-PSA% in clinical practice and for interpreting the data correctly, the advantages shown have to be considered along with the potential limitations of f-PSA%. Int. J. Cancer 74:630–636.© 1997 Wiley-Liss, Inc.     

PSAD和游离/总PSA比值在前列腺癌诊断中的意义

 目的　比较研究前列腺特异抗原(PSA)、PSA密度(PSAD)和游离/总PSA比值(F/TPSA)在前列腺癌诊断中的价值。方法　41例前列腺增生和22例前列腺癌患者,术前用放免法测定血清PSA和游离PSA。所有患者经直肠腔内B超测出前列腺体积,求得PSAD,用t检验比较分析。结果　前列腺癌组的PSA、PSAD均显著高于前列腺增生组(PSA：46.3±33.8μg/Lvs7.04±6.91μg/L,P=0.000021;PSAD：1.43±1.21μg。L-1。ml-1vs0.14±0.15ng。ml-1。ml-1,P=0.000055)。两组的F/TPSA比值无显著差异(0.18±0.11vs0.22±0.18,P=0.34)。结果　PSA和PSAD是鉴别前列腺癌的良好指标,对于PSA可疑者,PSAD有助于区分前列腺癌和前列腺增生,本组游离/总PSA比值不能帮助鉴别诊断。     

Biology of prostate-specific antigen.

Prostate-specific antigen (PSA) is an androgen-regulated serine protease produced by both prostate epithelial cells and prostate cancer (PCa) and is the most commonly used serum marker for cancer. It is a member of the tissue kallikrein family, some of the members of which are also prostate specific. PSA is a major protein in semen, where its function is to cleave semenogelins in the seminal coagulum. PSA is secreted into prostatic ducts as an inactive 244-amino acid proenzyme (proPSA) that is activated by cleavage of seven N-terminal amino acids. PSA that enters the circulation intact is rapidly bound by protease inhibitors, primarily alpha1-antichymotrypsin, although a fraction is inactivated in the lumen by proteolysis and circulates as free PSA. This proteolytic inactivation, as well as the cleavage of proPSA to PSA, is less efficient in PCa. Serum total PSA levels are increased in PCa, and PSA screening has dramatically altered PCa presentation and management. Unfortunately, although high PSA levels are predictive of advanced PCa, a large fraction of organ-confined cancers present with much lower total PSA values that overlap those levels found in men without PCa. Measurement of free versus total PSA can increase specificity for PCa, and tests under development to measure forms of proPSA may further enhance the ability to detect early-stage PCa. PSA is also widely used to monitor responses to therapy and is under investigation as a therapeutic target. Finally, recent data indicate that there may be additional roles for PSA in the pathogenesis of PCa.