[Show abstract][Hide abstract] ABSTRACT: To determine the validity of using complexed prostate-specific antigen (cPSA) levels for diagnosing biochemical recurrence after radical prostatectomy (RP).
With linear regression modelling, we determined threshold cPSA levels for biochemical recurrence in patients after RP for clinically localized prostate cancer. We calculated sensitivity, specificity, predictive values, and likelihood ratio tests of each threshold for diagnosing biochemical recurrence using total PSA (tPSA) as the reference standard.
In the regression models, tPSA and cPSA were highly correlated (r = 0.99). For the diagnosis of biochemical recurrence, tPSA thresholds of 0.20 and 0.40 ng/mL corresponded to cPSA thresholds of 0.12 ng/mL (95% confidence interval 0.08-0.17) and 0.29 (0.22-0.28) ng/mL, respectively. For the detection of biochemical recurrence, a cPSA threshold of 0.12 ng/mL had a sensitivity of 96%, specificity of 88%, positive predictive value of 89%, negative predictive value of 88%, positive likelihood ratio of 8, and negative likelihood ratio of 0.05; the respective values for a cPSA threshold of 0.29 ng/mL were 96%, 96%, 96%, 96%, 24 and 0.04.
cPSA has high validity for the diagnosis of biochemical recurrence after RP. Pending external validation, cPSA might be useful for biochemical surveillance after RP.
BJU International 05/2007; 99(4):758-61. · 3.05 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Adiponectin is a polypeptide hormone produced by adipocytes that has anti-angiogenic properties. Circulating adiponectin is lower in obese men. Obesity has been associated with advanced stage and a higher risk of biochemical progression following radical prostatectomy (RP) in several series. We examined whether serum adiponectin is associated with advanced disease stage at RP.
Adiponectin was measured by enzyme-linked immunosorbent assay in the preoperative serum of 236 men treated with RP between 1998 and 1999. The odds ratio (OR) of advanced stage (pT3a or greater) and high grade disease (pathological Gleason sum 7 or greater) associated with quartiles of adiponectin were estimated using multivariate logistic regression models.
Serum adiponectin weakly correlated inversely with body mass index (Spearman r = -0.22, p = 0.01). Serum adiponectin was not associated with cancer stage or grade. However, in normal weight men adiponectin was positively associated with high stage disease (OR 1.14, 95% CI 1.02 to 1.29, p = 0.03), although there was no statistically significant association with high grade disease (OR 1.05, 95% CI 0.94 to 1.18, p = 0.38). In overweight and obese men adiponectin was inversely associated with high grade disease (OR 0.94, 95% CI 0.87 to 1.01, p = 0.09), although there was no statistically significant association with high stage disease (OR 0.97, 95% CI 0.91 to 1.04, p = 0.43). Further adjustments for body mass index had little impact on any ORs.
These data provide evidence to suggest that adiponectin may be related to prostate cancer aggressiveness, although the direction of the associations may depend on the extent of adiposity and on cancer grade.
The Journal of Urology 11/2005; 174(4 Pt 1):1266-70. · 3.75 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Obesity has been associated with a higher risk of progression following radical prostatectomy (RP). Obese men have higher serum leptin, a hormone produced by adipocytes, which has also been shown to be an in vitro prostate cancer growth factor. We examined whether serum leptin correlates with advanced pathological findings at RP.
Preoperative serum from 225 men treated with RP between 1998 and 1999 was examined for serum leptin. Multivariate logistic regression analysis was used to determine whether serum leptin was predictive of extraprostatic extension (pT3a).
Serum leptin highly correlated with body mass index (Spearman r = 0.602, p <0.001). Serum leptin was not associated with total or percent free prostate specific antigen (PSA), biopsy or prostatectomy Gleason score, age or height. On multivariate analysis with total and percent free PSA, clinical stage, age, biopsy Gleason score, body mass index, serum leptin, and height as variables considered for entry into the model, serum PSA (p = 0.009), clinical stage (p = 0.019) and serum percent free PSA (p = 0.041) were the only variables predictive of extraprostatic extension. Serum leptin was not significantly associated with pathological stage (pT3a).
In the current study of predominantly white men with mainly low risk disease there was no statistically significant association between serum leptin and pathological stage (pT3a) at RP. In this cohort serum leptin was not a good biomarker for predicting advanced stage at RP.
The Journal of Urology 04/2005; 173(3):773-6. · 3.75 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Numerous studies have assessed serum total PSA (tPSA) levels among different races. We extended the serum biomarker profiling using prostate-specific antigen (PSA) derivatives in age-matched screening populations that included white, black, and Korean-American patients. The median ages were 61 years for white and black patients and 63 years for Korean-American patients. Serum samples from 70 men in each ethnic group were analyzed using 3 different tPSA assays (Tosoh AIA 600II, Bayer Immuno-1, Roche Elecsys 2010). The percentage of free PSA (fPSA) was measured directly by Roche Elecsys 2010 immunoassay and then calculated from complexed PSA (cPSA) and tPSA results determined with the Bayer Immuno-1. The percentage of cPSA was determined using cPSA and tPSA assayed by the Immuno-1 method. Statistical analyses included nonparametric Kruskal-Wallis and analysis of variance (ANOVA) evaluations. There were no differences noted in the tPSA values based on ANOVA among the 3 races irrespective of the assay platform methodology employed. Also, the PSA derivatives, percentages of fPSA and cPSA, evaluated using the Kruskal-Wallis test, showed no significant differences for either derivative assayed on 2 different assay platforms among the 3 groups. In a contemporary screening population comparing tPSA, percentage of fPSA, and percentage of cPSA levels in 3 races, there were no significant differences identified among the groups.
[Show abstract][Hide abstract] ABSTRACT: Measurement of human kallikrein 2 (hK2) has improved early detection and staging of prostate cancer. However, reported concentrations of hK2 among currently used assays have not been standardized in any way. We compared two hK2 assays and five different recombinant hK2 variants (rhK2) and suggest a common calibrator as an important step and putative reference substance in hK2 assay standardization.
We measured 146 sera by two hK2 assays, using assay-specific calibrators to assess the difference between the two assays. Serial dilutions of five rhK2 preparations were measured repeatedly, with one preparation assigned as calibrator and the others as unknowns to define which variant provided the closest match between the two assays. This rhK2 variant was used to recalibrate both assays. We measured hK2 concentrations in the same 146 patients to evaluate the change in the difference.
Use of assay-specific calibrators for comparison of the two assays yielded a Deming regression equation of: y = 0.789 (95% confidence interval, 0.674-0.922)x + 0.014 (0.004-0.025) micro g/L; R(2) = 0.667. Analysis of five rhK2 variants revealed that the enterokinase (ek)-rhK2 form provided the best match between both assays. Using the ek-rhK2 as a common calibrator, we observed a change in the slope of the regression curve to: y = 1.106 (0.872-1.340)x + 0.006 (-0.002 to 0.016) micro g/L; R(2) = 0.648, suggesting an increase in the mean estimate of agreement between the two assays.
Calibration with a common calibrator substantially increased agreement between the assays. The ek-rhK2 variant provided the best performance of all tested rhK2 variants and should undergo mass spectrometry and amino acid analysis for exact mass determination and value assignment to evaluate its potential as a reference material for immunoassays for hK2.
[Show abstract][Hide abstract] ABSTRACT: A detailed understanding is evolving as to how androgen receptor (AR) functions as a transcriptional regulator via its binding to androgen response elements (ARE) within promoter and enhancer regions of prostate-specific differentiation markers such as PSA, hK2, and PSMA. It has been assumed that an understanding of regulation of expression of these marker proteins would also provide an understanding of the mechanisms whereby AR interactions regulate proliferation and survival of malignant prostate cells. In order to validate this hypothesis, we used a series of human prostate cancer models [i.e., LAPC-4, CWR22Rv1, MDA PCA-2b, LNCaP, and C4-2B (derived from LNCaP)] to test whether there is a consistent concordance between androgen responsive regulation for malignant growth vs. regulation of expression of prostate differentiation specific markers PSA, hK2, and PSMA.
In order to define androgen growth responsiveness in vivo, human prostate cancer cell lines were inoculated as xenografts into intact vs. surgically castrated adult male nude mice and the subsequent tumor growth response monitored. To assess androgen regulation of PSA and hK2 expression in these cell lines, the concentration of PSA and hK2 in the conditioned standard media and charcoal stripped media +/- androgen from each cell line was determined using an immunoassay system. PSMA enzymatic activity was determined using the PSMA substrate (3)H N-acetylaspartylglutamate ((3)H NAAG).
Wild-type AR expressing LAPC-4 cells are androgen responsive for their in vivo growth. This cell line is also androgen sensitive for the expression of both PSA and hK2 in vitro and express PSMA. CWR22Rv1 cells have a mutated AR and are androgen responsive for growth in vivo and androgen sensitive for hk2 but not PSA expression. CWR22Rv1 produce approximately 1.4-fold more PSA, approximately 18-fold more hK2, and have 21-fold higher PSMA activity than LAPC-4 cells. MDA PCA-2b cells are androgen responsive for growth in vivo and androgen sensitive for PSA expression. MDA PCA-2b cells produce approximately 250-fold more PSA but almost equivalent amounts of hK2 compared to LAPC-4 and have approximately 19-fold higher PSMA activity. Both late passage LNCaP and C4-2B are androgen independent for growth in vivo but remain androgen sensitive for both PSA and hK2 expression. LNCaP cells produce approximately 50-fold more PSA, approximately 35-fold more hK2, and have 28-fold higher PSMA activity compared to LAPC-4. C4-2B cells produce approximately 80-fold higher levels of PSA, approximately 250-fold higher levels of hK2. C4-2B also the highest PSMA activity of the cell lines with 105-fold higher PSMA activity than LAPC-4 and approximately 4-fold higher activity than late passage LNCaP cells.
Androgen can coordinately regulate both the tumor growth and expression of prostate specific marker genes as observed for the LAPC-4 human prostate cancer cells. Such coordinated regulation, however, is not universal. In all of the other cell lines, there is a dissociation between androgen responsive regulation of malignant growth vs. regulation of expression of prostate specific markers PSA and hK2. In addition, PSMA activity in these cell lines increases as cells become more androgen independent for growth in vivo. These results emphasize that tumor growth and the expression of the specific secretory genes are independently regulated molecular events even if they share a requirement for androgen and/or AR function. Additional independent mechanisms occur in prostate cancer cells for regulation of expression for even the highly related PSA and hK2 genes. Further studies are needed to clarify the mechanisms for androgen ligand-independent, AR-dependent regulation of the genes that directly effect the growth of androgen (i.e., ligand) independent prostate cancer cells. Unfortunately, the data in this present report do not validate the use of the PSA or hK2 gene as surrogates for a model system for such critically important mechanistic studies. Prostate prostate cancer cells. Unfortunately, the data in this present report do not validate the use of the PSA or hK2 gene as surrogates for a model system for such critically important mechanistic studies.
The Prostate 04/2003; 54(4):249-57. · 3.84 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Prostate-specific antigen (PSA) exists in human serum in two principal forms, free PSA (fPSA) and protein-complexed PSA, predominantly PSA-ACT (alpha(1)-antichymotrypsin). Equimolar response (EMR) total PSA (tPSA) immunoassays measure each of these forms equally while skewed-response (SKR) assays overestimate or underestimate the tPSA concentration. The advantages of EMR over SKR tPSA assays are controversial.
We used five nonhuman serum-based samples each containing a different proportion of fSPA:PSA-ACT (0:100 to 100:0, %:%) and patients' serum samples from men with histologically confirmed benign prostatic hyperplasia (BPH) (n=94) or PCA (n=30) and a wide range of fPSA concentrations to investigate the molar response status of six tPSA assays. Receiver-operator characteristic (ROC) curve analysis was used to compare the discriminatory power of these assays in distinguishing men with BPH from those with PCA.
The Bayer Immuno-1 tPSA (BtPSA) assay demonstrated EMR characteristics and diagnostic accuracy similar to the Hybritech Tandem-E and Tandem-R tPSA assays. At 90% sensitivity, EMR tPSA assays had higher specificity than SKR tPSA assays.
The BtPSA assay is an EMR tPSA assay and EMR assays provide improved diagnostic specificity over SKR tPSA assays.
[Show abstract][Hide abstract] ABSTRACT: Differences in stability of the free and complexed molecular forms of prostate-specific antigen (PSA) may influence the clinical utility of assays for these forms, as well as the calculated ratios to total PSA (tPSA), such as percent free PSA (fPSA) and percent complexed PSA (cPSA). The objective of this study was to directly compare the short-term stability of fPSA and cPSA under different storage conditions. Specimens (3 with prostate cancer, 3 biopsy-negative without cancer, 2 normal) from 8 men were analyzed at baseline within 2 hours of collection, and at 4 hours, 8 hours, 24 hours, 48 hours, and 1 week after storage at room temperature, 4 degrees C, or -20 degrees C. Serum specimens were analyzed in duplicate on the Bayer Immuno 1 analyzer (tPSA, cPSA) and on the Beckman Coulter Access analyzer (tPSA, fPSA Tandem assays). Baseline tPSA values ranged from 0.7 to 62.0 ng/mL, with a median of 7.9 ng/mL (Immuno 1). Overall, all forms of PSA were stable up to 24 hours at the 3 temperatures, with the exception of fPSA and percent fPSA, which decreased when stored at 4 degrees C. After 1 week, tPSA levels decreased when stored at room temperature and at 4 degrees C, as did cPSA stored at room temperature. Over the 7 days, percent cPSA was stable at room temperature, but increased at 4 degrees C. There were no significant changes in any PSA form or calculated ratio with storage at -20 degrees C for up to 1 week. In summary, in the short term (<1 week), fPSA is less stable with storage than tPSA or cPSA in a time- and temperature-dependent fashion. Thus, specimen handling should be considered when interpreting PSA results. It is recommended that specimens not analyzed the same day (within 8 hours of collection) be stored frozen at -20 degrees C.
[Show abstract][Hide abstract] ABSTRACT: Over time, the parameters commonly used to predict pathological stage in men with localized prostate cancer have changed, and there is now little stratification in pretreatment prostate-specific antigen (PSA) concentrations, clinical stages, and biopsy Gleason scores. This prospective study evaluated the utility of complexed PSA (cPSA ) for predicting organ-confined disease in a contemporary series of subjects. The age range of the 420 men was 39 to 72 years (58.2 +/- 6 years). Specimens were collected before radical prostatectomy, and total and free PSA (Hybritech Tandem assays, Beckman Access; Beckman Coulter, Inc., Brea, CA) and total and cPSA (Bayer Immuno 1; Bayer Corporation, Tarrytown, NY) were measured. Pathologic stage was determined from the prostatectomy specimen. Of the 420 men, 316 (75%) had organ-confined disease, and 104 (25%) had non-organ-confined disease (20.7% had extraprostatic extension, 2.6% had seminal vesicle involvement, and 1.4% had positive lymph nodes). Prebiopsy Gleason score distribution was as follows: organ-confined organ-confined, 6 (87%) and 7 (10%); non-organ-confined, 6 (66%) and 7 (30%). Of patients with organ-confined disease, 75% had clinical stage T1c disease compared with 56% for non-organ-confined disease. Using univariate logistic regression, the following variables predicted organ-confined disease: biopsy Gleason score, clinical stage, total PSA, percent free PSA, cPSA, percent cPSA (P <0.05). A multivariate model with biopsy Gleason score, clinical stage, and cPSA had a receiver operator characteristic area under the curve of 0.69. Replacing cPSA with total PSA in this model provided similar information. cPSA and total PSA were highly correlated (r = 0.985). In summary, cPSA was equivalent to total PSA in predicting organ-confined disease. Present and future models and nomograms using PSA as an indicator of pathological stage could consider use of cPSA.
[Show abstract][Hide abstract] ABSTRACT: Determining serum total prostate specific antigen (PSA) has proved to be a valuable diagnostic aid for detecting prostatic carcinoma, although the lack of specificity has limited its usefulness. Studies indicate that the use of percent free PSA would improve specificity while maintaining sensitivity. Since complexed PSA represents the major proportion of measurable PSA in serum, we determined whether it represents a single test alternative to the use of percent free PSA for the early detection of prostate cancer.
Archival serum was obtained from 385 men with no evidence of malignancy on biopsy and 272 with biopsy confirmed prostate cancer. We determined the concentration and proportion of total, complexed and free PSA.
Receiver operating characteristics analysis using total PSA results from all samples (range 0.32 to 117 ng./ml.) indicated that the areas under the curve for complexed PSA alone as well as the free-to-total and complexed-to-total PSA ratios were similar and significantly greater than those for total PSA alone. Within the range of 85% to 95% sensitivity receiver operating characteristics analysis revealed that the specificity of complexed PSA was higher than that of total PSA and equivalent to that of the free-to-total PSA ratio. We noted a similar improvement in specificity in the 4 to 10 ng./ml. total PSA range. Using published cutoff values for complexed, total and percent free PSA when total PSA was in the 4 to 10 ng./ml. range the sensitivity and specificity of complexed and percent free PSA were similar. Within the 4 to 10 ng./ml. total PSA range the population of patients with no evidence of malignancy and complexed PSA below the upper limit was different with respect to total PSA from that with no evidence of malignancy and free PSA greater than 25%.
The measurement of complexed PSA represents an alternative to the use of percent free PSA, although the patient populations identified by the 2 tests are different.
The Journal of Urology 06/2000; 163(5):1476-80. · 3.75 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Thrombomodulin (TM), a marker of endothelial cell damage, has been localized to the placental syncytiotrophoblast. A prospective cohort study of twenty-five pregnant women who were admitted with a clinical diagnosis of placental abruption was undertaken. Abruption was confirmed after delivery in eight cases (Group 1). Group 2 consisted of seventeen patients with no clinical or pathologic evidence of placental abruption after delivery. TM was significantly elevated in Group 1 (71.59+/-5.35 vs. 48.29+/-3.53 ng/ml, p = 0.001). The sensitivity and specificity of TM > or =60 ng/ml as a marker for abruption was 87.5 and 76.5%, respectively. In comparison, the sensitivity of an abnormal coagulation profile, maternal Kleihauer-Betke and ultrasound in patients with abruption was 0, 16.7 and 28.6%, respectively. TM is a highly sensitive and specific marker for acute placental abruption.
Thrombosis and Haemostasis 02/1999; 81(1):32-4. · 5.76 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The influence of radical prostatectomy on the hypothalamic pituitary axis has not been well studied. It is also unclear how alterations in serum androgen levels that result from surgical removal of the prostate might influence the recovery of libido and sexual function following radical prostatectomy. We determined the influence of radical prostatectomy on the hypothalamic pituitary testicular axis of 63 men with clinically localized prostate cancer treated only with radical prostatectomy.
A total of 63 healthy men 43 to 67 years old were enrolled in this prospective study. Phlebotomy was performed immediately before and 1 year following radical retropubic prostatectomy. Sera were stored frozen and analyzed as a group at the end of the study. We measured serum testosterone, percent free testosterone, dihydrotestosterone (DHT), estradiol, luteinizing hormone (LH), follicle-stimulating hormone (FSH), sex hormone binding globulin and prolactin.
Following radical prostatectomy there was a statistically significant increase in serum testosterone, free testosterone, estradiol, LH and FSH (p <0.0001), and statistically significant decrease in serum DHT (p <0.0001). No difference was noted in serum sex hormone binding globulin or prolactin levels. There was no statistically significant correlation between any serum hormone and sample storage time, patient age or prostate volume that could limit potential bias in study design. Serum hormone changes did not correlate with pathological stage or histological grade for this group of patients.
Radical prostatectomy influences the hypothalamic pituitary axis by increasing serum testosterone, percent free testosterone, estradiol, LH and FSH while decreasing serum DHT levels. These findings suggest that the sexual dysfunction associated with radical prostatectomy cannot be explained by androgen deficiency alone. These data further suggest that the normal prostate and/or prostate neoplasm could secrete a substance or substances that give negative feedback control to pituitary gonadotropin secretion. Further investigation is warranted to identify this substance or substances.
The Journal of Urology 08/1998; 160(2):449-53. · 3.75 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Aims of the study: Retrospective studies investigating the use of percent free-PSA for early detection of prostate cancer were limited for various reasons: by their use of long-term stored sera, poor mix of non-cancer to cancer cases and the use of only men with PSA values between 4.0 and 10.0 ng/mL. This prospective study investigates the clinical utility of percent free-PSA and complexed-PSA for early detection of prostate cancer in 219 consecutive men presenting for prostate biopsy. Methods: Of 246 consecutive men who underwent ultrasound guided sextant biopsy of the prostate for PSA elevation and/or suspicious digital rectal exam, 219 men had serum total PSA levels between 2.0 and 20.0 ng/mL and were included in this study. Serum total, free and complexed (PSA-ACT) were measured (Hybritech Inc.). Results: Pathologic examinations demonstrated that 72% and 28% of the biopsies were non-cancer and cancer respectively. The mean percent free-PSA was statistically different between the groups (cancer 14%+/-6.4 and non-cancer 18+/-9%, P<0.001) and improved cancer detection. PSA-ACT provided only modest improvement in cancer detection over that of total PSA. Among this cohort of men, the optimal total PSA reflex range for percent free-PSA was 3.0-7.0 ng/mL (38% specificity) with a percent free-PSA cut-off of 20% (95% sensitivity) yet only affected 56% of the cases. Conclusions: PSA-ACT added very little additional value to the clinical utility of total PSA for early detection. Percent free-PSA performed well for all reflex ranges. A sensitivity and specificity of 95% and 20% respectively were obtained using a single cut-off of 25% for percent free-PSA for the group of men with total PSA values between 4.0 and 10.0 and correlated well with recently reported prospective analyses.
Prostate cancer and prostatic diseases 07/1998; 1(4):197-203. · 2.10 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To begin to identify new tumor markers, we recently performed a systematic study of gene expression in cancers of the colon and pancreas. Of the 45,000 genes identified, 183 were found to be expressed at significantly elevated levels in pancreatic cancer. One of the genes was tissue inhibitor of metalloproteinase type I (TIMP-1), which encodes a secreted protein. Analysis of TIMP-1 serum levels revealed significant increases in pancreatic cancer patients, but TIMP-1 by itself was inadequate as a serum marker for cancer. However, a combination of individually suboptimal markers (TIMP-1, CA19-9, and carcinoembryonic antigen) detected 60% of 85 patients with pancreatic cancers in a highly specific manner. These results suggest that a systematic analysis of gene expression can reveal novel serum markers and that individually suboptimal markers can be combined to yield higher sensitivity and specificity.
[Show abstract][Hide abstract] ABSTRACT: A retrospective clinical study was conducted to compare results obtained by AxSYM(R) CA 15-3(TM), IMx(R) CA 15-3 and Truquant(R) BRTM RIA using surplus serum specimens from healthy volunteers and patients with benign and malignant diseases. Linear regression analysis of AxSYM and IMx CA 15-3 versus Truquant BR RIA for specimens with results 0-250 U/ml gave correlation coefficients of 0. 888 and 0.910 and slopes of 0.67 and 0.69, respectively. For specimens with results 0-2,000 U/ml, slopes were 0.95 and 0.91, respectively. Receiver operator characteristic analyses, based on results from healthy females plus nonmalignant disease patients versus breast cancer patients, for all three assays gave essentially equivalent areas under the curves. Concordance between AxSYM or IMx CA 15-3 and Truquant BR RIA was greater than 92%. Serial dilution of seven serum specimens yielded linear regression correlation coefficients ranging from 0.997 to 1.000 for AxSYM and IMx CA 15-3, and from 0.962 to 0.998 for Truquant BR RIA. The average percent CVs of the calculated assay values for the 7 specimens were 4.9, 2.7 and 18.1 for AxSYM CA 15-3, IMx CA 15-3 and Truquant BR RIA, respectively. Average percent recoveries ranged from 96.2 to 110.7 for AxSYM and IMx CA 15-3, and 81.8 to 93.3 for Truquant BR RIA. Although assay values differ between the two methodologies, AxSYM CA 15-3, IMx CA 15-3 and Truquant BR RIA showed comparable trending results for the 24 breast cancer patients evaluated for serial monitoring.
[Show abstract][Hide abstract] ABSTRACT: The Bayer Immuno 1 PSA Assay measures total PSA in human serum and demonstrates excellent performance with an interassay CV < or = 3.4% and a biological detection limit of 0.03 microgram/L. No significant interference from common hormonal and chemotherapeutic drugs, kallikrein, prostatic acid phosphatase, and trypsin, or elevated levels of total bilirubin, hemoglobin, triglycerides, and IgG was observed. The 95th percentile values for healthy individuals increased with age from 3.0 micrograms/L for males 50-59 years and 3.3 micrograms/L for males 60-69 years, to 4.6 micrograms/L for males > or = 70 years. Clinical studies with retrospective samples demonstrated correspondence between serial measurements of PSA and clinical outcome for 98% of 159 prostate cancer patients. Clinical sensitivity for patients with clinical evidence of disease, untreated at the time of specimen draw, increased with increasing stage from 77.5-100%. Specificity of 60-70% for BPH and other benign urogenital diseases was consistent with previous findings. Bayer Immuno 1 PSA Assay values for 2131 specimens from healthy subjects and patients with prostate cancer, BPH, and other malignant and nonmalignant diseases correlated well with the Abbott IMx PSA Assay over the range 0.0-6,238 micrograms/L (Y = 1.10 x + 0.02). The Bayer Immuno 1 PSA Assay provides automated ultrasensitive, precise, and equimolar measurement of total PSA in human serum.