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Prostatic acid phosphatase, beta-glucuronidase and prostate specific antigen assays in fine needle aspirates from benign and malignant prostates.

Enzymatic assays for tartrate-sensitive acid phosphatase and beta-glucuronidase, and radio-immunoassay for prostate-specific antigen, were modified for application to fine-needle aspirate samples from benign and malignant human prostates. When compared to samples from benign prostates, the ratio of acid phosphatase to beta-glucuronidase activities was significantly decreased in needle aspirates from malignant prostates. Prostate-specific antigen values in the aspirates did not correlate with malignancy.

Acid Phosphatase↗

Free and complexed prostate-specific antigen serum ratios to predict probability of primary prostate cancer and benign prostatic hyperplasia.

OBJECTIVES: Ratios of free to total prostate-specific antigen (f/t PSA ratio) improved differentiation of benign prostatic hyperplasia (BPH) from prostate cancer (CaP). Using sera obtained at least 1 month prior to biopsy-confirmed diagnosis and logistic regression adjusted for disease prevalence, probability curves are constructed to predict the presence of CaP. METHODS: The patient population included 122 (44%) BPH sera and 155 (56%) prostate carcinoma sera collected prior to any therapy. The total PSA range = 2.0-20.0 ng/mL; median age = 69 years. External reference standards for both free and total PSA assays were used to standardize the assays and correct the ratio. Probability curves and tables for cancer incidence were formulated for a subset of the total test population (total PSA range = 2.0-10.0 ng/mL; 98 BPH, 118 CaP patients) by using logistic regression and prior cancer prevalence statistics derived from a published patient screening study. RESULTS: Median f/t PSA ratios were 0.18 and 0.12 in the overall sample and 0.19 and 0.12 in the subset for BPH and CaP, respectively (P = 0.0001). The median total PSA concentrations for BPH and CaP were 5.8 and 6.7 ng/mL when total PSA range = 2.0-20.0 ng/mL and were 4.9 and 5.9 ng/mL when total PSA range = 2.0-10.0, respectively. CONCLUSIONS: Cancer probability curves were constructed to help guide decisions concerning biopsy and other aspects of prostate cancer disease management. Further validation of this approach in another series of patients is necessary and is planned.

Adult↗

Free to total prostate-specific antigen (PSA) ratio improves the discrimination between prostate cancer and benign prostatic hyperplasia (BPH) in the diagnostic gray zone of 1.8 to 10 ng/mL total PSA.

OBJECTIVES: Improved discrimination between prostate cancer (PC) and benign prostatic hyperplasia (BPH) is clearly needed. Our aim in this study was to evaluate whether the free to total prostate-specific antigen (PSA) ratio would be useful in the gray zone of 1.8-10 ng/mL total PSA range. METHODS: In a consecutive series of 435 clinic patients referred for prostate evaluation, 308 had a total PSA < 10 ng/mL (92 had PC and 216 BPH). Free and total PSA were measured, and the free to total PSA ratio calculated. RESULTS: Total PSA values were significantly different between the two groups. For the 200 patients with a total PSA < 6 ng/mL, no significant difference in total PSA values were seen (P = 0.411), whereas free to total PSA ratios remained statistically different (P < 0.001). Receiver operating characteristic (ROC) curve analysis comparing the performances of total PSA over the ratio of free to total PSA showed a clear advantage for the ratio at all sensitivity levels. CONCLUSIONS: These data demonstrate that in a significant number (n = 308) of prostatic patients in the diagnostic gray zone of 1.8-10 ng/mL total PSA, the routine use of free to total PSA might be advantageous in discriminating between cancer and benign hyperplasia. This advantage remained for total PSA < 4 ng/mL. Further study is warranted to confirm these findings in an unselected population.

Aged↗

Normal range prostate-specific antigen versus age-specific prostate-specific antigen in screening prostate adenocarcinoma.

OBJECTIVES: Prostate-specific antigen (PSA) has become the most useful serum tumor marker in the diagnosis and screening of prostate adenocarcinoma. The currently cited reference range of normal (0 to 4.0 ng/mL monoclonal) lacks both the sensitivity and specificity to be universally accepted as a screening test, and alternatives to serum PSA have been proposed, such as PSA density, PSA velocity, and age-adjusted PSA. Age-adjusted PSA takes into account the facts that as men grow older the prostate enlarges and that screening should have maximum sensitivity in younger men and maximum specificity in older men. METHODS: A population of 4,710 men with no known history of prostate adenocarcinoma underwent 5,629 examinations by transrectal ultrasound of the prostate (TRUS) from 1987 to 1994. This population consists of Mobile Urology Group, Mobile, Alabama, and Emory University, Atlanta, Georgia, patient databases. We have examined our data to determine the sensitivity, specificity, and positive predictive values for normal range PSA (0 to 4 ng/mL) versus age-specific PSA values. RESULTS: A total of 2040 patients had an abnormal digital rectal examination (DRE) and 3581 procedures were performed for an elevated PSA and a normal DRE. Biopsies were performed in 2,657 patients with 945 (35.6%) positive for cancer. Criteria for biopsy included elevated PSA (more than 4 mg/mL), PSA density more than 0.15 abnormal DRE, or suspicious TRUS. Patients were grouped according to decade: group 1 (ages 40 to 49 years, n = 183), group 2 (ages 50 to 59 years, n = 1018), group 3 (ages 60 to 69 years, n = 2358), and group 4 (ages 70 to 79 years, n = 1687). CONCLUSIONS: Use of the age-specific range for PSA increases the sensitivity in younger men more likely to benefit from treatment, and decreases the biopsy rate in older patients who may not be candidates for aggressive treatment. Age-adjusted PSA is the most valuable for patients over the age of 70 years of whom 22% would be spared TRUS with biopsy.

Adenocarcinoma↗

Predictors of prostate cancer on repeat prostatic biopsy in men with serum total prostate-specific antigen between 4.1 and 10 ng/mL.

OBJECTIVES: We determine whether the different molecular forms of prostate-specific antigen (PSA) and other PSA variables can predict prostate cancer in men undergoing repeat prostate needle biopsy. METHODS: Between 1997 and 2001, repeat biopsy was performed in 97 patients who had undergone prior negative prostate biopsy. The ability of total PSA (tPSA), complexed PSA (cPSA), free PSA (fPSA), free-to-total PSA (fPSA/tPSA), free-to-complexed PSA (fPSA/cPSA), complexed-to-total PSA (cPSA/tPSA), tPSA density (tPSAD), cPSA density (cPSAD), transition zone tPSA density (tPSATZ) and transition zone cPSA density (cPSATZ) was assessed by univariate and multivariate analyzes as well as receiver operating characteristics (ROC) curves. RESULTS: Prostate cancer on repeat biopsy was detected in 24% of subjects (23 of 97) who had a negative initial biopsy. The PSA parameters cut-off to ensure a 96% sensitivity of cancer detection, were 29% using fPSA/tPSA, 32% using fPSA/cPSA, 0.18 ng/mL/cc using tPSATZ and 0.16 ng/mL/cc using cPSATZ. The fPSA/tPSA would have prevented 32% of negative biopsies, the fPSA/cPSA 28%, the tPSATZ 23% and the cPSATZ 30%. ROC curve analysis fPSA/tPSA, fPSA/cPSA ratios, tPSATZ and cPSATZ were significantly better predictors of repeat biopsy results than tPSA or cPSA, but there was no significant difference in the ROC curves among these four PSA parameters. In the multivariate logistic regression analysis these four PSA parameters were significant predictors for cancer detection in the repeat biopsy group (P < 0.001). CONCLUSION: fPSA/tPSA ratio, fPSA/cPSA ratio, tPSATZ and cPSATZ enhance the specificity of PSA testing compared to tPSA or cPSA when determining which patients should undergo repeat biopsy.

Aged↗

Free and complexed prostate specific antigen in the differentiation of benign prostatic hyperplasia and prostate cancer: studies in serum and plasma samples.

PURPOSE: We prospectively evaluated serum and plasma concentrations of total and free prostate specific antigen (PSA), and PSA complexed to alpha1-antichymotrypsin in 170 patients who underwent biopsy, including 59 with prostate cancer and 111 with benign prostatic hyperplasia. We compared the usefulness of the ratios of free-to-total and complexed-to-total PSA for distinguishing between prostate cancer and benign prostatic hyperplasia, and studied the influence of blood clotting on the ratios. MATERIALS AND METHODS: Blood samples were processed to generate serum and citrated plasma. To calculate complexed-to-total and free-to-total PSA we assayed plasma and serum samples for total and complexed PSA using homemade immunoassays, and total and free PSA using the Immulite assay. The 2 total PSA assays were compared using the Tandem-E PSA assay. Receiver operating characteristics curves were constructed for the total population, and for 2 to 20, 4 to 20, 2 to 10 and 4 to 10 ng./ml. total PSA. RESULTS: In all groups complexed-to-total PSA had higher specificity than free-to-total and total PSA, especially at 90 to 100% sensitivity. Generally citrated plasma samples provided higher specificity than serum samples for all sensitivity values. The best performance for complexed-to-total and free-to-total PSA was obtained in the subset of patients in whom total PSA was 2 to 10 ng./ml. CONCLUSIONS: Our results indicate that the complexed-to-total PSA ratio performed better for classifying disease status than the free-to-total PSA ratio in the whole patient population and in the diagnostic gray zone of 2 to 10 ng./ml. In addition, plasma samples should be used to calculate the complexed-to-total and free-to-total PSA ratio.

Aged↗

The value of the measurement of serum prostate specific antigen in patients with benign prostatic hyperplasia and untreated prostate cancer.

Serum prostate specific antigen (PSA) levels were measured in 139 patients with benign prostatic hyperplasia (BPH) and in 88 patients with prostate cancer who were managed by deferred treatment. Acute urinary retention and large prostate glands tended to be associated with high PSA levels, but at levels greater than 10 ng/ml there was a significant risk of carcinoma being found on subsequent histological examination. The risk of progression of untreated prostate cancer was associated with levels of PSA greater than 20 ng/ml and with a high rate of change of PSA level. The value of measuring PSA in these patients is discussed.

Aged↗

Urethral metastasis from prostatic carcinoma as diagnosed by immunoperoxidase technique using prostate-specific antigen and prostate-specific acid phosphatase.

A rare case of urethral metastasis from prostatic adenocarcinoma is reported. Ordinary histological examination by hematoxylin and eosin staining could not determine whether the primary site was the prostate or the urethra. However, with an immunoperoxidase technique using prostate-specific acid phosphatase and prostate-specific antigen as markers for prostatic cells, we obtained a precise diagnosis of the primary sites. As a result, the patient could be successfully treated with hormonal therapy.

Acid Phosphatase↗

Prostate-specific antigen and prostate acid phosphatase in the detection of early prostate cancer and the prediction of regional lymph node metastases.

Serum values of prostate-specific antigen (PSA) and prostatic acid phosphatase (PAP) were determined in 180 patients prior to pelvic lymphadenectomy and radical prostatectomy and in 40 patients prior to pelvic lymphadenectomy alone. In all tumor stages, PSA was superior to PAP in detecting cancer of the prostate. By PSA determination using a cutoff level of 4 ng/ml (Tandem assay), 28.8% of the patients with prostate cancer, stage pT2pN0M0, and 17.8% of the cases with a stage pT3pN0M0 tumor could not be detected. All these tumors had been noticed, however, by digital rectal examination. This indicates that PSA determination cannot replace digital rectal examination as a screening method for prostate cancer. In this study, it was possible neither by PSA nor by PAP to define a practicable cutoff level for patients with and without lymph node metastases. A clear differentiation between the stages pT2pN0M0 and pT3pN0M0 was not possible by either PSA or PAP alone.

Acid Phosphatase↗

Prostate-specific antigen and prostatic acid phosphatase in the detection of early prostate cancer and in the prediction of regional lymph node metastases.

Serum values of prostate-specific antigen (PSA) and prostatic acid phosphatase (PAP) were determined in 180 patients prior to pelvic lymphadenectomy and radical prostatectomy and in 40 patients prior to pelvic lymphadenectomy alone. In all tumor stages, PSA was superior to PAP in detecting cancer of the prostate. By PSA determination using a cutoff level of 4 ng/ml (Tandem assay), 28.8% of the patients with prostate cancer, stage pT2pN0M0, and 17.8% of the cases with a stage pT3pN0M0 tumor could not be detected. All these tumors had been noticed, however, by digital rectal examination. This indicates that PSA determination cannot replace digital rectal examination as a screening method for prostate cancer. In this study, it was possible neither by PSA nor by PAP to define a practicable cutoff level for patients with and without lymph node metastases. A clear differentiation between the stages pT2pN0M0 and pT3pN0M0 was not possible by either PSA or PAP alone.

Acid Phosphatase↗

Transcript profiling of the androgen signal in normal prostate, benign prostatic hyperplasia, and prostate cancer.

Human prostate adenocarcinoma (CaP) and benign prostatic hyperplasia (BPH) have epithelial and stromal cell origins, respectively. To determine whether the androgen signal is processed differently in these cell types the expression of transcripts for enzymes that control ligand access to the androgen receptor (AR) were measured. Transcripts for type 2 5alpha-reductase, ketosteroid reductases [aldo-keto reductase (AKR)1C1-AKR1C4], the major oxidative 3alpha-hydroxysteroid dehydrogenase (HSD) retinol dehydrogenase (RODH)-like 3alpha-HSD (RL-HSD) and nuclear receptors [AR, estrogen receptor (ER)alpha, and ERbeta] were determined in whole human prostate and in cultures of primary epithelial cells (PEC) and primary stromal cells (PSC) from normal prostate, CaP and BPH by real-time RT-PCR. Normal PEC (n=14) had higher levels of AKR1C1 (10-fold, P<0.001), AKR1C2 (115-fold, P<0.001) and AKR1C3 (6-fold, P<0.001) than normal PSC (n=15), suggesting that reductive androgen metabolism occurs. By contrast, normal PSC had higher levels of AR (8-fold, P<0.001) and RL-HSD (21-fold, P<0.001) than normal PEC, suggesting that 3alpha-androstanediol is converted to 5alpha-dihydrotestosterone to activate AR. In CaP PEC (n=14), no significant changes in transcript levels vs. normal PEC were observed. In BPH PSC (n=21) transcripts for AR (2-fold, P<0.001), AKR1C1 (4-fold, P<0.001), AKR1C2 (10-fold P<0.001), AKR1C3 (4-fold, P<0.001) and RL-HSD (3-fold, P<0.003) were elevated to increase androgen response. Differences in the AR:ERbeta transcript ratios (eight in normal PEC vs. 280 in normal PSC) were maintained in PEC and PSC in diseased prostate. These data suggest that CaP may be more responsive to an ERbeta agonist and BPH may be more responsive to androgen ablation.

20-Hydroxysteroid Dehydrogenases↗

Steroid-involved transcriptional regulation of human genes encoding prostatic acid phosphatase, prostate-specific antigen, and prostate-specific glandular kallikrein.

We have compared the steroid regulation of human genes encoding prostatic acid phosphatase (hPAP), prostate-specific antigen (hPSA), and prostate-specific glandular kallikrein (hK2) at the level of transcription. Reporter constructs of hPAP promoter covering the region -734/+467 were functional in both prostatic (LNCaP and PC-3) and nonprostatic (CV-1) cell lines in transient transfections. hPAP -231/+50 with eight identified transcription factor-binding sites showed the highest, and hPAP -734/+467 showed the lowest transcriptional activity in CV-1 cells. The hPAP promoter could not be induced with androgen, glucocorticoid, or progesterone, contrary to the hPSA (-620/+40) and hK2 (-493/+27) promoters in PC-3 cells cotransfected with the respective steroid receptor expression vector. Therefore, steroids cannot directly regulate hPAP gene expression via receptor binding to steroid response elements at -178 and +336, which have been shown to have androgen receptor-binding ability in vitro. Glucocorticoid was the most powerful activator of the hPSA construct at 10-nM steroid concentrations. On the contrary, glucocorticoid stimulation of the transcriptional activity of the hK2 construct was the weakest among the tested steroids. The results indicate that the steroid response elements in the proximal promoters of hPSA and hK2 genes are not androgen specific, offering the molecular basis for the expression of these genes outside the prostate in tissues containing steroid receptors.

Acid Phosphatase↗

Serum prostate specific antigen levels in men with benign prostatic hyperplasia and cancer of prostate.

OBJECTIVE: To determine the sensitivity, specificity and positive predictive value of the PSA test at the conventional cut-off value of 4 ng/ml. DESIGN: Retrospective study. SETTING: Nairobi Hospital Laboratory, Nairobi. DATA SOURCE: Results of serum Prostate specific Antigen (PSA), estimation and prostate histology specimens at the Nairobi Hospital Laboratory between January 1997 and December 1999. RESULTS: A total of 3309 PSA tests and 524 prostate biopsies were processed during the study period. One hundred cases had both PSA test and histology, where the PSA test was done before the surgical procedure. Forty nine of them had histological diagnosis of cancer of prostate (CAP) while 71 had benign prostate hyperplasia (BPH). There was considerable overlap in the PSA concentrations between the two groups, the ranges being 0.34-36 ng/ml and 1.78-4339 ng/ml for BPH and CAP respectively. 63.4% of BPH subjects had PSA concentrations above the 4 ng/ml threshold value; 29.6% being in the diagnostic gray zone of 4-10 ng/ml. In contrast only 6% of CAP subjects had PSA values in the gray zone. Using the 4 ng/ml cut-off, the sensitivity, specificity and positive predictive value of the PSA test were 89.8, 37 and 49% respectively. CONCLUSION: Although PSA is a sensitive test, it is not sufficiently specific to discriminate between BPH and CAP at intermediate values. Additional approaches are required to enhance its specificity for CAP screening without reducing the sensitivity.

Humans↗

[Characterization of prostate cancer, benign prostatic hyperplasia and normal prostates using endorectal 1H magnetic resonance spectroscopy].

BACKGROUND: We evaluate the usefulness of 1H endorectal resonance spectroscopy to characterize prostate pathology. METHODS: With an endorectal surface coil we have studied 20 individuals with normal (1), benign hyperplastic (9) and malignant (10) prostates. RESULTS: The major findings of our studies were that the patients with cancer have a significantly lower citrate-to-choline ratio (cit/cho) and creatin-to-choline ratio (cre/cho) than the patients with BPH (p < 0.05). There is well correlation between cit/cho and gland-to-stroma ratio of the BPH tissue as well as histological grade of the cancer tissue. 1H spectroscopy offers the advantages of differential diagnosis between benign and malignant prostates. We, however, failed to demonstrate cancer in 2 cases; the lesion was too small in one case, and out of the region of interest in the other. It is necessary that the foci in the prostate is at least 1.5 X 1.5 X 1.5 cm3 of the volume in order to obtain genuine spectrogram of carcinoma. CONCLUSION: Endorectal 1H magnetic resonance spectroscopy can characterize metabolic differences between the normal and malignant prostate.

Adult↗

Prostate specific antigen and prostatic acid phosphatase measurements for the follow-up of patients with prostate cancer.

The clinical application of 84 prostate specific antigen (PSA) and prostatic acid phosphatase (PAP) measurements for the follow-up of 36 patients with treated prostate cancer was retrospectively examined by case study. Clinicians use several risk markers including serum levels of PSA and PAP to monitor prostate cancer progression or stability. These results of PAP and PSA tests were either utilized during the patient's clinical assessment or they were disregarded. In either case, the results would support or counter the physician's clinical decision for patient management. After predictive value analysis it was concluded that measurement of PSA alone is more useful than parallel measurements of PSA and PAP, when utilized together with standard criteria for assessing treated prostate cancer patients.

Acid Phosphatase↗

[A comparison between prostate-acid-phosphatase and prostate-specific antigen in the diagnosis of prostatic carcinoma].

A comparison is made of prostatic acid phosphatase (PAP) and prostate specific antigen (PSA) in the diagnosis of prostatic carcinoma. In a retrospective study PAP ans PSA were compared in 127 normal elderly men, in 187 patients with benign prostatic hyperplasia (BPH) and in 162 patients with untreated prostatic carcinoma. In the control group a normal value of 2.2 micrograms/l was found for PAP and 5.0 micrograms/l for PSA. In 41% of BPH patients the PSA level was higher than 5.0 micrograms/l. Because of this substantial percentage a cut-off value of 10 micrograms/l was used instead of 5.0 micrograms/l. In the BPH group 20% had a PSA level over 10 micrograms/l and 21% a PAP over 2.2 micrograms/l. Of the carcinoma patients without metastasis 57% had a PSA level over 10 micrograms/l and of those with metastatic disease, 92%. For PAP these percentages were 35 and 77, respectively. It is concluded that PSA is a more sensitive tumour marker than PAP.

Acid Phosphatase↗

Response of prostate volume, prostate-specific antigen, and testosterone to flutamide in men with benign prostatic hyperplasia.

Patients diagnosed as having benign prostatic hyperplasia (BPH) had determination of prostate volume (PV), prostate-specific antigen (PSA), and serum testosterone before consideration for entry into a double-blind, randomized trial of flutamide (750 mg/day for 6 months). The mean PSA level for these patients (N = 43) was 7.6 ng/ml (range: 1.0 to 45.7), and the mean PV was 76.8 cm3 (range: 24 to 198). Linear regression analysis demonstrated a strong correlation between the two (r = 0.876, P less than 0.05). Every 10 cm3 of prostate volume accounted for 1.02 ng/ml of PSA in the serum. Twenty-two patients (11 treated with flutamide, 11 with a placebo) agreed to enter the study. Prostate volume decreased by 35% and PSA by 65% (P less than 0.001) within 6 months. These changes occurred despite a 58.3% increase in serum testosterone levels (P less than 0.01). Patients treated with a placebo experienced no significant changes. Side effects were minimal, and flutamide was well tolerated. These data suggest that androgen deprivation therapy with flutamide may be an effective and safe treatment for BPH.

Aged↗

[Prostatic carcinoma: immunoperoxidase study with antisera against prostatic acid phosphatase and the prostate-specific antigen].

An immunoperoxidase study in 19 patients with cancer of prostate, using antiserums directed against prostatic acid phosphatase (PAP) and prostate specific antigen (PSA), allowed classification of tumors as strongly, moderately and poorly differentiated, and undifferentiated forms. Tests were conducted on specimens fixed and embedded in paraffin wax. Evaluation of degree of positivity for cells most marked by PAP and by PSA failed to establish its correlation with tumoral differentiation. Results, in fact, showed that poorly differentiated or undifferentiated forms of prostatic carcinoma contained cells with enhanced positive reactions when compared with strongly differentiated forms. Morphologically strongly differentiated forms showed weaker positivity than observed in normal prostate, this positivity being relatively homogeneous throughout the zone of proliferation, and cells varied little in their degree of positivity. Characteristic findings in less well differentiated forms were several strongly positive cells, with marked differences in positivity between cells and frequent alternating positive and negative zones. These findings may be of particular interest for diagnostic interpretation of strongly or poorly differentiated forms.

Acid Phosphatase↗