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Evaluation of prostate-specific antigen and prostatic acid phosphatase as prostate cancer markers.

Prostate-specific antigen (PSA) and prostatic acid phosphatase (PAP) have been evaluated in patients with prostate cancer, benign prostatic hypertrophy (BPH), and prostatitis. PSA has proved to be diagnostically more sensitive than PAP for the detection of prostate cancer: 95.0 per cent vs 60.0 per cent for 40 newly diagnosed cancer cases, and 97.1 per cent vs 65.7 per cent for 35 relapsed cases. This also holds true for those patients with early-stage disease: 71.4 per cent vs 0 per cent for 7 Stage A1 cases. The specificities of PSA and PAP are comparable, 96.8 per cent vs 98.9 per cent, respectively. PSA is also more sensitive for monitoring therapy, since it usually rises before PAP and always precedes clinical signs of relapse. Although PSA may be elevated more frequently than PAP in some patients with BPH and prostatitis, it is postulated that these patients with elevated serum PSA and normal serum PAP may fall into a high-risk sub-population which may have early prostate cancer or precancerous conditions not easily detectable by current clinical and diagnostic techniques. Our data suggest PSA is a sensitive useful tumor marker for the diagnosis and management of prostate cancer. In addition, PAP, in combination with PSA, may serve as a useful adjunct for differential diagnosis and confirmation of advanced stage prostate cancer.

Acid Phosphatase↗

Relationship between Prostatic Specific Antigen (PSA) and volume of the prostate in the Benign Prostatic Hyperplasia in the elderly.

Increase of the Prostatic Specific Antigen (PSA) is a non-invasive, sensitive and specific markers for prostatic diseases, including prostatic cancer. However, age-related Benign Prostatic Hyperplasia (BPH), as well as prostatitis, may at the same time alter PSA values. The aim of this study was to evaluate the relationship between ageing and PSA, and whether age-specific upper normal limits of PSA should be considered for elderly patients. We evaluated 569 consecutive subjects aged 60 years or more (mean age 74.2 years) who were free from malignant prostatic disease, without clinical evidence of prostatic phlogosis and who were not receiving PSA levels affecting drugs. All patients underwent Digital Rectal Examination (DRE) and Trans-Rectal Ultrasonography (TRU), with determination of the three prostatic diameters, the Maximum Adenoma Diameter (MAD) and calculation of the prostatic volume (PV) by the ellipsoid formula. PSA was determined in all patients before DRE and TRU, and the PSA free ratio was determined in those with total PSA values >4 ng/ml. The PSA density was calculated according to the formula PSA/PV. One hundred and seventy-nine subjects (31.6%) were found to have PSA values >4 ng/ml: among them, 26 (14.5%) had values exceeding 10 ng/ml. Age was slightly correlated with PV (P<0.05), but not with PSA values. On the contrary, PSA values were strongly related with PV and MAD (P<0.01 both). Mean PSA-free ratio was 16.3+/-6.0% and most of patients had values in the so-called 'grey zone' of discrimination between benignity and malignity. Elevated PSA levels are common in older subjects without evidence of prostatic malignancy; PSA values are poorly affected by age itself and strongly correlated with increasing PV. These results suggest the possibility to consider as indicative of benignity PSA values between 4 and 10 ng/ml, when these values are associated with relevant increase of PV and with PSA-free ratio greater than 10%.

Age Factors↗

Changes in the endocrine environment of the human prostate transition zone with aging: simultaneous quantitative analysis of prostatic sex steroids and comparison with human prostatic histological composition.

BACKGROUND: It is well-known that the incidence of benign prostatic hyperplasia (BPH) increases with aging. The age-dependent changes in the ratio of serum sex steroid concentrations may play a role in BPH development. To clarify the relationship between the prostatic tissue concentrations of these steroids and age, we established a precise method of simultaneous quantitative analysis for prostatic sex steroids and used this method to investigate the tissue concentrations of three major sex steroids (testosterone, dihydrotestosterone, and estradiol) in the human prostate. METHODS: The methodology for the simultaneous quantitative analysis of prostatic sex steroids was established using castrated rat prostatic tissue, coupled with internal standards, for androgen-deprived medium, and the validation of the method was examined. Human prostatic tissues were collected during surgery and immediately frozen at -70 degrees C. Using our method, the steroidal fractions were extracted, purified, and quantified. The proportions of stroma, epithelium, and glandular lumen were measured on each histological specimen, using an image analyzer. RESULTS: The validation tests showed that our method of quantitative analysis was precise and sensitive enough for the quantification of testosterone, dihydrotestosterone, and estradiol in the prostate. In humans, the prostatic dihydrotestosterone concentration decreased with age, but the concentrations of testosterone and estradiol showed no relation with age. Therefore, the ratio of estradiol to dihydrotestosterone concentration (E2/DHT) in prostate increased with age. The E2/DHT ratio showed a significant positive correlation with the proportion of stroma. CONCLUSIONS: The age-dependent decrease in prostatic dihydrotestosterone and constant estradiol concentration lead to a relatively estrogen-dominant environment compared to that at younger ages. We assume that this relatively estrogen-dominant status induces stromal proliferation by some mechanism and leads to the development of BPH.

Aged↗

[Significance of prostatic acid phosphatase, gamma-seminoprotein and prostatic specific antigen in the urine. First report: the measurement of PAP, gamma-Sm and PA in the urine of patients with prostatic diseases].

To study the significance of prostatic acid phosphatase (PAP), gamma-seminoprotein (gamma-Sm) and prostatic specific antigen (PA) in urine, we have determined the urinary levels of these proteins in women and infants, in patients without prostatic disease, in patients with benign prostatic hypertrophy, and in patients with prostatic adenocarcinoma. Women and infants were found to excrete little PAP (27.9 +/- 4.8 ng/mg) and undetectable levels of gamma-Sm except one case, and undetectable levels of PA in the urine. The excretion of PAP in patients with prostatic carcinoma who were either castrated, or treated with endocrine therapy was lower than the levels in women and infants, or the levels in patients without prostatic diseases, or the levels in patients with BPH. Urinary excretion levels of gamma-Sm and PA were undetectable in the patients with well-controlled prostatic carcinoma. The present study suggests that the determination of PAP, gamma-Sm and PA in the urine of patients with prostatic carcinoma may become a useful tool for monitoring of the primary locus of the carcinoma, but additional assays of urinary PAP, gamma-Sm and PA should be measured at regular intervals to be concluded.

Acid Phosphatase↗

Relationship of prostate-specific antigen and prostate volume in patients with biopsy proven benign prostatic hyperplasia.

BACKGROUND: Emerging data suggest a direct correlation between prostate-specific antigen (PSA) and prostate volume in patients with lower urinary tract symptoms (LUTS) and clinical evidence of benign prostatic hyperplasia (BPH). We attempt to confirm that a similar correlation exists between PSA and prostate volume in patients with biopsy-proven BPH. METHODS: Over a 5 year period, 2,270 patients were confirmed to have BPH as the only histological diagnosis after evaluation with serum PSA, trans-rectal ultrasound (TRUS) biopsy, and prostate volume measurement. PSA and prostate volume were statistically analyzed by age-stratified cohorts, including multiple regression analysis and assessment of correlation using the Pearson correlation coefficient (r). RESULTS: Mean PSA and prostate volume increased with each advancing cohort of age, and the correlation of PSA and prostate volume was determined to be statistically significant (P < 0.001) in each cohort with a correlation coefficient ranging from 0.33 to 0.41. CONCLUSIONS: We confirm that the relationship between PSA and prostate volume in a large series of patients with biopsy-proven BPH provides a comparable correlation to data for patients with LUTS and clinical BPH. As such, PSA represents a valuable approximation of prostate volume, and may prove to be clinically useful in the management of patients with BPH.

Adult↗

Prostate specific antigen cannot distinguish stage T1a (A1) prostate cancer from benign prostatic hyperplasia.

To determine if serum prostate specific antigen (PSA) has decreased the prevalence of stages T1a (A1) and T1b (A2) prostate cancer, and to compare the PSA values for patients with stages T1a and T1b prostate cancer and men with symptomatic benign prostatic hyperplasia, 966 patients undergoing transurethral resection of the prostate were evaluated retrospectively. Included in the study population were 499 consecutive patients who underwent transurethral resection of the prostate for obstructive urinary symptoms in 1986 (no PSA group), and 467 consecutive patients who underwent resection in 1989 and 1990 who were evaluated with serum PSA preoperatively (PSA group). The mean age for the no PSA group was 71 years compared to 70 years for the PSA group (p = 0.36). The overall prevalence of stages T1a and T1b prostate cancer in the no PSA group was 8.6% compared to 10.3% in the PSA group (p = 0.37). The prevalence of stages T1a and T1b prostate cancer in the no PSA group was 3.6% and 5.0%, respectively, compared to 7.3% and 3.0%, respectively, for the PSA group (p = 0.01). In the PSA group the median PSA value for patients with stages T1a and T1b prostate cancer was 3.8 ng/ml compared to 3.4 ng/ml for the patients without cancer (p = 0.59). The median PSA level for the stage T1a cancer patients was 2.4 ng/ml, which was not statistically different from that in patients without cancer (p = 0.31), and the median PSA level for the stage T1b cancer patients was 5.9 ng/ml, which was statistically different than that in patients without cancer (p = 0.01). These findings suggest that the routine use of serum PSA does not decrease the prevalence of stage T1a prostate cancer and that PSA may decrease the prevalence of stage T1b tumors but a larger study would be necessary to document this finding.

Adult↗

Lack of value of radioimmunoassay for prostatic acid phosphatase as a screening test for prostatic cancer in patients with obstructive prostatic hyperplasia.

We examined the incidence of prostatic cancer in patients with an elevated radioimmunoassay for prostatic acid phosphatase and clinical benign prostatic hyperplasia on digital rectal examination. Of 295 patients screened with prostatic acid phosphatase tests 17 fulfilled the criteria of having an elevated prostatic acid phosphatase, clinically benign prostate and histological examination of the prostatectomy specimen. None of the 17 patients had histological evidence of prostatic cancer. The results confirm the predictions of mathematical models that prostatic acid phosphatase is of no practical value as a screening test for prostatic cancer in patients with clinical benign prostatic hyperplasia.

Acid Phosphatase↗

Comparison of three assays for total serum prostate-specific antigen and percentage of free prostate-specific antigen in predicting prostate histology.

OBJECTIVES: To determine the statistical performance of three different assays for prostate specific antigen (PSA) and the percentage of free PSA with respect to the differentiation of histologic benign prostatic hyperplasia (BPH) and prostate cancer in men who underwent surgical removal of prostate tissue. METHODS: Serum of 86 men scheduled for prostate surgery (transurethral resection of the prostate [TURP], simple open prostatectomy, radical prostatectomy, cystoprostatectomy) was frozen and subjected to measurement in batches using three different assays for total PSA (Hybritech Tandem-E, Abbott IMx, Tosoh AIA-600) and free PSA by the Hybritech method after a single freeze-thaw cycle. The histologic diagnosis of the removed tissue (35 BPH and 51 cancer) was used as a "gold standard" for classification of disease status. Sensitivity, specificity, positive and negative predictive values, and diagnostic efficiency were calculated for the three total PSA assays and the free/total PSA ratios for the entire cohort and subsets. Receiver-operating characteristic (ROC) curve analysis was used to compare the performance of the assays and ratios. RESULTS: Mean and median total PSA values differed slightly between the three assays for all patients, and for those with BPH and cancer, but this difference was not significant. Because of a considerable overlap, the differences between the mean PSA values for men with BPH and prostate cancer were not significant. At a cutpoint of 4.0 ng/mL, sensitivity with respect to the differentiation between BPH and prostate cancer was 68.6% for all three total PSA assays; the respective AUCs (0.613-0.625) were not significantly different. While the performance of the free/total PSA ratios was superior, the differences were only significant when subsets of patients were considered with a total PSA between 4 and 10 ng/mL or 4 and 15 ng/mL (AUCs 0.789-0.816). Likewise, sensitivity, specificity, and diagnostic efficiency was better in these subsets of patients. CONCLUSIONS: In this study in which a "gold standard" based on histologic analysis of the entire (or large part of) the prostate gland was used to classify disease status, the three assays for total serum PSA (Hybritech Tandem-E, Abbott IMx, and Tosoh AIA-600) performed very similarly with identical sensitivities (at a cutpoint of 4.0 ng/mL) and comparable AUCs with respect to the differentiation of men with histologic BPH and prostate cancer. The ratios of free/total PSA calculated as free PSA by the Hybritech manual immunoradiometric assay (IRMA) method over all three total PSA assays, performed marginally better in the entire patient population. However, in the subsets of patients with a PSA of 4-10 ng/mL and 4-15 ng/mL, all three ratios performed significantly better than the three total PSA assays. The proper choice of a cutpoint for the ratio (15%, 17%, 19%, or 21%) depends on the desirability of maximizing either sensitivity or specificity while optimizing diagnostic efficiency.

Adult↗

Citrate as an in vivo marker to discriminate prostate cancer from benign prostatic hyperplasia and normal prostate peripheral zone: detection via localized proton spectroscopy.

OBJECTIVES: This study was designed to determine whether citrate levels detected by localized 1H spectroscopy could reliably discriminate regions of prostate adenocarcinoma from surrounding regions of normal peripheral zone and benign prostatic hyperplasia (BPH). METHODS: In 28 patients and 5 volunteers stimulated echo proton spectroscopy was used in conjunction with endorectal surface coils to obtain water-suppressed 1H spectra from regions of normal prostate peripheral zone, BPH, and prostate cancer. 1H spectra from prostate cancer patients were correlated with pathologic areas identified on T2-weighted endorectal coil magnetic resonance (MR) images and histologic study of the step-sectioned gland after surgery. RESULTS: The major finding of in vivo studies was consistently lower citrate levels in prostate cancer compared with BPH and normal prostate peripheral zone. This was reflected by significantly (P < 0.05) lower mean citrate/(creatine plus choline) peak area ratio observed for regions of cancer (0.67 +/- 0.17) compared with BPH (1.21 +/- 0.29) and normal peripheral zone (1.46 +/- 0.28). Moreover, there was no overlap of individual cancer and normal peripheral zone citrate ratios and no significant difference between citrate ratios in regions of normal peripheral zone in young volunteers (1.28 +/- 0.14) and age-matched patients (1.46 +/- 0.28). The observed alterations in vivo citrate levels were supported by citrate concentration data obtained from extracts of histologically proven samples of normal, benign, and malignant prostatic tissues removed at surgery. In vitro citrate levels in the normal peripheral zone (30.9 +/- 8.5 mumol/g wet weight) and BPH (46.3 +/- 5.4 mumol/g wet weight) were significantly higher than those for prostate cancer (3.74 +/- 0.54 mumol/g wet weight). CONCLUSIONS: These studies further demonstrate the potential of citrate as an in vivo marker for discriminating prostate cancer from surrounding regions of normal peripheral zone and BPH.

Adenocarcinoma↗

A lectin histochemistry comparative study in human normal prostate, benign prostatic hyperplasia, and prostatic carcinoma.

The partial oligosaccharide sequences of glycoconjugates and the nature of their glycosidic linkages were investigated in normal human prostate, benign prostatic hyperplasia (BPH) and prostatic carcinoma by means of lectin histochemistry, using light microscopy and Western blot analysis. The labeling pattern of BPH differed from that of normal prostate in having more intense staining with DSA, HPA, UEA-I and AAA, and in showing lesser staining with WGA and SBA. Prostatic carcinoma differed from normal prostates in displaying the more intense labeling with PNA, DSA, SBA, DBA, UEA-I and AAA, and in having lesser labeling with WGA. The main differences in labeling pattern between prostatic carcinoma and BPH were that the latter specimens showed more marked staining with PNA, DSA, DBA, SBA, UEA-I and AAA, and lesser staining with WGA and HPA. The staining patterns of SNA, MAA, ConA, LCA and GNA were similar in all three groups of specimens. For most of the lectins studied, including those showing a similar immunohistochemical staining in the three groups of specimens studied, the Western blot analysis showed differences in the banding pattern among normal, hyperplastic, and carcinomatous prostates. Present results suggest that the glycosylation of proteins was modified in both BPH and prostatic carcinoma. In BPH a strong expression of N-acetylgalactosamine residues occurred, while in prostatic carcinoma an increase of sialic acid, galactose and fucose residues was observed. No changes in mannose residues were detected.

Adult↗

The clinical utility of measuring free-to-total prostate-specific antigen (PSA) ratio and PSA density in differentiating between benign prostatic hyperplasia and prostate cancer.

OBJECTIVE: To evaluate the role of free-to-total prostate-specific antigen ratio (f/tPSA), prostate volume and PSA density in differentiating between men with prostate cancer and benign prostatic hyperplasia (BPH). PATIENTS AND METHODS: The study comprised 51 patients who were assessed after transurethral electroresection of the prostate (16 with prostate cancer and 35 with BPH). Patients with a tPSA of < or = 4.0 ng/mL and > or = 30.0 ng/mL were excluded from the analysis. Total and fPSA were measured using an immunoradiometric assay and prostate volume was determined by transrectal ultrasonography. The incidence of prostate cancer and BPH was then compared with the PSA variables to determine specificity and predictive value. RESULTS: Most patients with BPH had a tPSA of 4.0-6.0 ng/mL; no patients with BPH had a tPSA of > 20.0 ng/mL. Most patients with prostate cancer had a f/tPSA of 6-10%. The area under the receiver operating characteristic curve for f/tPSA was significantly greater than that for tPSA (P < 0.003). CONCLUSIONS: The measurement of f/tPSA and PSA density increase the specificity of the differential diagnosis between BPH and prostate cancer.

Aged↗

The correlation between clinical outcome and residual prostatic weight ratio after transurethral resection of the prostate for benign prostatic hyperplasia.

OBJECTIVE: To assess in a prospective study the use of a new variable, the residual prostatic weight ratio (RPWR), for evaluating the clinical outcome after transurethral resection of the prostate (TURP). PATIENTS AND METHODS: From April 1996 to June 1997, 40 men (mean age 70.4 years, range 53-85) with symptomatic benign prostatic hyperplasia were evaluated using the American Urological Association (AUA) symptom score, measurements of the mean and maximum urinary flow rate (Qave and Qmax), and by transrectal ultrasonography (TRUS) before and 16 weeks after TURP. The estimated total prostate weight was derived as 0.52 x length x width x height x the specific gravity of the prostate (1.010). The RPWR was calculated as the prostate weight after TURP divided by the initial weight, where the value after TURP was the initial weight minus that of the TURP specimen. The clinical outcome was evaluated by the difference (Delta) in AUA score, Qmax and Qave before and 16 weeks after surgery. RESULTS: There was a close correlation between the estimated prostate weight and the actual weight of the TURP specimen (r = 0.82 and 0.80 for the adenoma and total prostate, respectively). The mean (SD) RPWR, DeltaAUA score, DeltaQmax and DeltaQave were 50.1 (17.1)%, 11.5 (5. 3), 9.0 (4.2) mL/s and 6.2 (2.9) mL/s, respectively. There was a negative correlation between the RPWR and the DeltaAUA, DeltaQmax and DeltaQave (r = -0.81, -0.68, and -0.70, respectively, P < 0.05). The prostate volume estimated by TRUS decreased significantly 16 weeks after TURP. CONCLUSIONS: TRUS is a useful tool for estimating prostate weight before surgery. The smaller the RPWR at 16 weeks after TURP, the better the clinical outcome.

Aged↗

Relationship between prostate specific antigen, prostate volume and age in the benign prostate.

The relationship between prostate specific antigen (PSA) levels, prostate volume and age was examined in 472 men who underwent PSA assay (Hybritech), digital rectal examination (DRE) and transrectal ultrasound (TRUS) as part of a community survey of benign prostatic hyperplasia following exclusion of men with prostate cancer. The mean age of the study population was 60 years (range 40-79). The mean PSA was 2.4 ng/ml and 85% of the men had levels < 4 ng/ml. There was a modest correlation between PSA and both age and prostate volume. The mean prostate and adenoma volumes were 32 ml (SD 13.4) and 15 ml (SD 10.7) respectively. Prostate volume increased with age. Linear regression analysis revealed an independent association between PSA and age when controlling for volume. The mean ratio of PSA per unit of prostate volume was 0.072 ng/ml. This ratio also increased with age. Age and prostate volume influences PSA levels independently. The sensitivity and specificity of PSA adjusted for volume and age in the diagnosis of prostate cancer need to be evaluated in association with DRE and TRUS.

Adult↗

Advantage of systematic random ultrasound-guided biopsies, measurement of serum prostate-specific antigen level and determination of prostate volume in the early diagnosis of prostate cancer.

Two hundred and sixteen patients, presenting with a suspicious digital examination (stage T3 excluded) or a level of prostate-specific antigen (PSA) greater than or equal to 2.5 ng/ml, assessed by radioimmunoassay, underwent a transrectal ultrasound examination. Prostate volume was systematically calculated and correlated to PSA level. Biopsies were performed: (1) on suspicious peripheral hypoechoic areas; ultrasound-guided biopsies; (2) systematically on the 2 prostate lobes, whatever the result of transrectal ultrasound imaging:random systematic ultrasound-guided biopsies. In the 186 patients who had never undergone prostate surgery, ultrasound-guided biopsies showed 42 prostate cancers and random systematic ultrasound-guided biopsies showed 75; 14 of the 76 patients with normal digital rectal examination and transrectal ultrasound imaging had a prostate cancer. In the 30 patients who had previously undergone surgery for benign prostatic hypertrophy, random systematic ultrasound-guided biopsies showed 18 prostate cancers, 13% more than ultrasound-guided biopsies; 75% of patients with a serum PSA greater than 5 ng/ml had a prostate cancer. A very significant correlation was found between PSA level and prostatic volume (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Antigens, Neoplasm↗

The combination of human glandular kallikrein and free prostate-specific antigen (PSA) enhances discrimination between prostate cancer and benign prostatic hyperplasia in patients with moderately increased total PSA.

BACKGROUND: Prostate-specific antigen (PSA) is the most reliable tumor marker available and is widely used for the diagnosis and management of prostate cancer. Unfortunately, PSA cannot distinguish efficiently between benign and malignant disease of the prostate, especially within the range of 4-10 microg/L. Among the refinements developed to enhance PSA specificity is the free/total PSA ratio, which is useful in discriminating between the two diseases within the diagnostic "gray zone". Recent data indicate that human glandular kallikrein (hK2), a protein with high homology to PSA, may be an additional serum marker for the diagnosis and monitoring of prostate cancer. METHODS: We analyzed 206 serum samples (all before treatment was initiated) from men with histologically confirmed benign prostatic hyperplasia (n = 100) or prostatic carcinoma (n = 106) with total PSA in the range of 2.5-10 microg/L. Total and free PSA and hK2 were measured with noncompetitive immunological procedures. Statistical analysis was performed to investigate the potential utility of the various markers or their combinations in discriminating between benign prostatic hyperplasia and prostatic carcinoma. RESULTS: hK2 concentrations were not statistically different between the two groups of patients. There was a strong positive correlation between hK2 and free PSA in the whole patient population. hK2/free PSA ratio (area under the curve = 0.69) was stronger predictor of prostate cancer than the free/total PSA ratio (area under the curve = 0.64). At 95% specificity, the hK2/free PSA ratio identified 30% of patients with total PSA between 2.5-10 microg/L who had cancer. At 95% specificity, the hK2/free PSA ratio identified 25% of patients with total PSA between 2.5 and 4.5 microg/L who had cancer. CONCLUSIONS: Our data suggest that hK2 in combination with free and total PSA can enhance the biochemical detection of prostate cancer in patients with moderately increased total PSA concentrations. More specifically, the hK2/free PSA ratio appears to be valuable in identifying a subset of patients with total PSA between 2.5 and 4.5 microg/L who have high probability of cancer and who should be considered for biopsy.

Aged↗

Prostate-specific membrane antigen levels in sera from healthy men and patients with benign prostate hyperplasia or prostate cancer.

Prostate-specific membrane antigen (PSMA) serum levels have been proposed to be of prognostic significance in patients with advanced prostate disease. The objective of the present study was to confirm PSMA serum expression by Western blot techniques, to determine whether such data could assist in the differentiation of benign from malignant prostatic disease, and to determine the suitability of serum PSMA measurements in predicting recurrent or progressive prostate malignancies. We measured PSMA, a transmembrane glycoprotein identified in prostate epithelial cells, in the sera of 236 normal individuals and cancer patients by Western blot analysis. Within the normal male population, PSMA levels increase with age and were found to be significantly elevated in subjects more than 50 years of age when compared to those of younger men. We did not confirm previous reports that serum PSMA measurements could distinguish late-stage prostate carcinoma from early-stage prostate carcinoma, nor did we find PSMA to be more effective than prostate-specific antigen in monitoring prostate cancer patient prognosis. Furthermore, we found elevated serum PSMA in healthy females, and, similar to the healthy male population, the levels increased with age, with the highest levels found in the sera from breast cancer patients. These latter observations further support that PSMA is not a specific biomarker for prostate cancer and that a variety of normal and diseased tissue may contribute to the serum levels of PSMA.

Adult↗

A prospective study to evaluate the role of complexed prostate specific antigen and free/total prostate specific antigen ratio for the diagnosis of prostate cancer.

PURPOSE: Patients are increasingly undergoing prostatic biopsy to identify localized prostate cancer. The decision to perform a biopsy is often made on the basis of total prostate specific antigen (PSA). However, this value lacks adequate specificity for this task. We evaluate the role that a number of these tests, including the Bayer complexed PSA (Bayer Diagnostics, Tarrytown, New York) and free/total PSA ratio, may have in our clinical practice. MATERIALS AND METHODS: A total of 160 consecutive patients attending a prostate assessment clinic were enrolled during an 18-month period in our study. All patients had a previously recorded total PSA (range 2.6 to 20.0 ng./ml.). Before transrectal ultrasound biopsy of the prostate gland, a blood sample was taken with patient consent. The findings on ultrasound were then recorded, including prostate volume. Serum samples were immediately sent for subsequent storage and analysis. RESULTS: Of the patients enrolled 109 had benign histology while 51 had prostatic carcinoma. The 2 patient groups were well matched for age. In our series patients with prostate cancer had significantly smaller prostates and higher mean total PSA. At a high sensitivity, such as 95%, it appeared that Bayer complexed PSA performed better than the other tests and ratios, with an estimated specificity of 24.8% compared with 17.4% for Bayer total PSA and 15.6% for Abbott free/total PSA (Abbott Laboratories, Abbott Park, Illinois). Receiver operator characteristics curves were drawn, and when the areas under them were calculated, we demonstrated that the area under the curve for Bayer complexed PSA (0.706) was between the values for total PSA (0.671) and free/total PSA ratio (0.731). However, the only statistically significant improvement in performance was in Bayer complexed PSA over the total PSA assays. CONCLUSIONS: Our study revealed that the overall diagnostic performance of Bayer complexed PSA appears to be better than the other PSA tests and ratios studied. The use of Bayer complexed PSA may lead to a reduction in the number of men undergoing unnecessary prostatic biopsy.

Aged↗

Expression of P-cadherin identifies prostate-specific-antigen-negative cells in epithelial tissues of male sexual accessory organs and in prostatic carcinomas. Implications for prostate cancer biology.

Cadherins constitute a family of calcium-dependent cell-cell adhesion molecules the individual members of which are essential for the sorting of cells into tissues during development. In this study, we examined the expression of E-cadherin, N-cadherin, and P-cadherin in tissues obtained from radical prostatectomies. Epithelial cells of prostatic glands, ejaculatory ducts, and seminal vesicles expressed E-cadherin but not N-cadherin. P-cadherin was expressed in epithelial cells of the seminal vesicles and ejaculatory ducts. In the prostate it was limited to the basal cells of prostatic acini, glands with basal cell hyperplasia, and atrophic glands denuded of the luminal cells. All P-cadherin-positive cells were negative for prostatic-specific antigen. Prostatic cancers were mostly P-cadherin negative, but some tumors had P-cadherin-positive areas frequently located close to ejaculatory ducts and negative for prostatic-specific antigen. The mutually exclusive expression of P-cadherin and prostatic-specific antigen suggests that these proteins are involved in differential mechanisms of cell regulation in prostate cancer. P-cadherin may become a useful marker in the diagnosis and management of patients with prostate cancer and low levels of prostatic-specific antigen.

Animals↗