Prostatic Acid Phosphatase Levels Research Articles

Conditions associated with normal levels of prostate-specific antigen and elevation of prostatic acid phosphatase.

Thirteen cases are reported with normal levels of prostate-specific antigen and elevated prostatic acid phosphatase (PAP). Conditions that were associated with an elevated PAP were myeloproliferative syndromes (four cases), metastatic nonprostatic carcinoma (six cases), prostatic carcinoma (one case), tuberculosis with a concurrent lupus-like syndrome (one case), and osteomyelitis (one case). The inclusion of PAP in the initial investigation of cases with suspected prostatic disease results in a decreased specificity.

The Characterization of Nonbacterial Prostatitis: Search for an Etiology

Nonbacterial prostatitis is often difficult to differentiate from other prostatic complaints and remains a vaguely characterized syndrome. Prostatic fluid inflammatory cells and elevated immunoglobulins raise the suspicion that this syndrome is caused by some undetected infection. Prostatic fluid antibodies against Chlamydia trachomatis, Ureaplasma urealyticum, staphylococcus, Staphylococcus faecalis, Bacteroides fragilis and Clostridium perfringens were measured in men with nonbacterial and bacterial prostatitis, and men without urinary symptoms by an enzyme-linked immunosorbent assay. Prostate specific antigen and prostatic acid phosphatase were measured in the prostatic fluid as indirect measures of secretory activity. Of 44 men with nonbacterial prostatitis 9 (20%) had detectable prostatic fluid antichlamydial antibody titers, compared with 3 of 25 control men (12%) and 2 of 13 (15%) with bacterial prostatitis—no evidence for a higher prevalence of pro static fluid antichlamydial antibody in men with nonbacterial prostatitis. Prostatic antibodies to the other organisms were rarely detected. When compared with unaffected men the low levels of prostate specific antigen and prostatic acid phosphatase, and more alkaline prostatic fluid in men with bacterial and nonbacterial prostatitis suggest that secretory dysfunction accompanies the inflammation. These data show that none of the organisms studied caused the majority of the cases of nonbacterial prostatitis and that either an agent as yet unidentified or multiple agents may be involved in the etiology of nonbacterial prostatitis.

Prognostic significance of changes in prostate-specific markers after endocrine treatment of stage D2 prostatic cancer.

The prognostic value was determined of prostate-specific antigen (PSA) and prostatic acid phosphatase (PAP) measured before and after endocrine treatment in 57 patients with newly diagnosed Stage D2 prostatic cancer. Therapy included orchiectomy or administration of luteinizing hormone releasing hormone analogues or an antiandrogen. The absolute pretreatment PSA (elevated in 100% of patients) but not PAP (abnormal in 93%) predicted disease progression (P < 0.0011), i.e., a poor response to therapy. Fifty-three patients responded to androgen deprivation with a decrease in PSA level. This declined to normal at 3 and 6 months in 25% of patients. Forty-nine percent had a greater than 90% decrease in their PSA level. By 1 year, 58% of patients had progressive disease. Both the nadir PSA level and the percent decline from the pretreatment level at 3 and 6 months predicted the progression-free interval (P < 0.001). Patients with a 90% or greater decline in PSA had a prolonged progression-free survival. Serial PAP levels were similarly prognostic. It was concluded that PSA was better than PAP in evaluating patients before and after androgen-deprivation therapy. The nadir level of both markers was an important tool to predict progression-free survival in patients with metastatic prostatic cancer.

Multicenter, Randomized, Double-Blind, Placebo Controlled Study to Investigate the Effect of Finasteride (MK-906) on Stage D Prostate Cancer

A total of 28 untreated patients with asymptomatic, stage D prostate cancer was randomized in a double-blinded fashion to receive finasteride (10mg. per day), a 5α-reductase inhibitor or placebo. Patients were evaluated at 3-week intervals by rectal examination, and serum prostate specific antigen (PSA) and prostatic acid phosphatase (PAP) levels, and at 6-week intervals by bone scan and transrectal ultrasound determinations of prostatic volume. Patients stopped the medication at week 6 at the discretion of the investigator when PSA levels increased from baseline. After 12 weeks all patients were reevaluated.Of the patients 13 received finasteride and 15 received placebo. The 2 groups did not differ statistically with respect to patient age, initial PSA and PAP level, or the extent of metastases on initial bone scan. A statistically significant decrease in the median percentage change from baseline in PSA at weeks 3 and 6 occurred in the finasteride group compared to the placebo group (−22.9% versus −2.9% and −15.1% versus +11.7%, respectively, p <0.05). Finasteride had no effect upon PAP, serum testosterone, prostatic volume or appearance of bone scans.A decrease in serum PSA in the finasteride treatment group suggests that finasteride exerts a minor effect in patients with prostate cancer. This effect does not approach that seen with medical or surgical castration yet because of the potency preserving feature and the lack of toxicity finasteride may warrant further study in the treatment of prostate cancer.

Long-term Clinical Study on Luteinising Hormone-releasing Hormone Agonist Depot Formulation in the Treatment of Stage D Prostatic Cancer

The results of long-term administration of leuprorelin acetate depot (TAP-144-SR), a sustained-release preparation of luteinising hormone-releasing hormone (LH-RH) agonist, to 40 stage D prostate cancer patients who had had no previous hormonal therapy, have been analyzed. The drug was administered by subcutaneous injection once every four weeks at a dose of 3.75 or 7.5 mg. The mean duration of treatment was 480 (141-1,266) days, and treatment continued for more than one year for 60% of the 40 patients. Objective response was evaluated in accordance with Japanese Response Criteria. The best objective response in the overall evaluation was a partial response in 68.6% of the total patient group (3.75 mg, 64.3%; 7.5 mg, 71.4%). During the administration period, 21 patients were diagnosed as having progressive disease (PD), and the mean time to onset of PD was 308 days. The earliest diagnoses of PD were made on bone metastases (17 cases) and prostatic acid phosphatase levels (12 cases). The survival rate, as determined by Kaplan-Meier's method, was 81.2% (3.75 mg, 80.5%; 7.5 mg, 81.3%) two years after starting the regimen and 66.0% (3.75 mg, 65.1%; 7.5 mg, 66.0%) after three years. There was no dose dependency between either of the two drug doses, which we adopted as functions of the objective response rate, and patients' survival. Serum levels of testosterone, LH and follicle-stimulating hormone (FSH) were monitored from the first-dose until the 148th week of administration. In all patients receiving the drug as scheduled, the testosterone level was maintained at less than 1 ng/ml, and the LH and FSH levels were maintained at levels lower than their respective upper normal limits. There were no particular adverse reactions specific to the long-term administration subsequent to the foregoing 12-week administration study. In conclusion, LH-RH analogue treatment is thought to be a long-lasting, effective, palliative measure for patients with previously-untreated, advanced, prostatic cancer.

Relationship between Prostatic Acid Phosphatase and Prostate-Specific Antigen Serum Levels and Prostatic Volume in Benign Prostate Hyperplasia

Serum levels of prostatic acid phosphatase (PAP) and prostate-specific antigen (PSA) were measured in 78 patients with benign prostate hyperplasia and compared with both the gland weight and the glandular component of prostatic tissue. Both PAP and PSA were significantly higher where prostate was heavier; however, we could not find a consistent factor which could correlate weight increase to marker levels. PSA tended to be higher when glandular component was more expressed. From the present findings we conclude that in patients with prostate cancer, PAP and PSA serum levels should be investigated considering also the benign components of prostate gland.

Regulation of prostatic carcinoma cell proliferation and secretory activity by extracellular matrix and stromal secretions

Previous studies from our laboratory have shown that reconstituted basement membrane and stromal secretory products are important regulators of benign prostatic epithelial cell growth and differentiation. In the present study we evaluated the impact of extracellular matrix (ECM) and soluble stromal secretory products on the proliferation and secretory activity of the androgen-responsive prostatic carcinoma cell line LNCaP. In these studies, dihydrotestosterone (DHT) was a potent mitogen for LNCaP cells cultured on plastic or on type I collagen. The growth response to DHT was greatly attenuated when LNCaP cells were grown on prostatic stromal ECM. Cells grown on stromal ECM also exhibited clustered morphology compared to the monolayer growth observed on plastic and secreted elevated levels of prostate specific antigen (PSA) and prostatic acid phosphatase (PAP). These findings indicate that cultivation of LNCaP on stromal ECM will promote the expression of differentiated functions. In additional studies, stromal cell conditioned medium (SCM) significantly increased PSA/PAP secretion by LNCaP cells in the presence of 10 nM DHT. The enhancement of DHT-induced PSA/PAP secretion by SCM was most pronounced when LNCaP cells were grown on stromal ECM. SCM did not significantly alter LNCaP proliferation. These studies indicate that prostatic stromal ECM and soluble secretory products will promote differentiated function in cultured LNCaP cells. In addition, we show that DHT can act as either a growth or differentiation-promoting stimulus depending on the presence of stromal factors.

Prediction of pelvic lymph node metastases by a prostate-specific antigen and prostatic acid phosphatase in clinical T3/T4M0 prostatic cancer.

Prostate-specific antigen (PSA) and prostatic acid phosphatase (PAP) were determined in the serum of 69 patients with clinical T3/T4M0 prostatic cancer before staging lymphadenectomy. In principle, high-dose radiotherapy was given only to patients of pathological N0 category. Seventeen patients had a prelymphadenectomy PSA level below the normal upper reference limit (10 micrograms/l) and only 3 of them had pelvic lymph node metastases. Fifteen of 52 patients with a preoperative PSA level > or = 10 micrograms/l were of N0 category. Only 8 of the 41 evaluable patients had PAP values above the normal range, and 6 of these 8 patients had pelvic lymph node metastases. Preoperative PSA values, but not preoperative PAP levels, assist the clinician in predicting regional lymph node metastases in patients with clinical T3/T4M0 prostatic cancer. Two-thirds of the patients with T3/T4 tumours and PSA values between 10 and 50 micrograms/l have regional lymph node metastases. About 80% of the patients with PSA levels < 10 micrograms/l belong to the N0 category. About 75% of the patients with PSA > 50 micrograms/l have N+ disease. Taking into account the individual preoperative PSA values, the indication for preradiotherapy staging lymphadenectomy should be balanced between the chance of demonstrating N+ disease, the expected postoperative morbidity and the benefit for the patient found to be of N0 category.

Prognostic Factors in Progression-Free Survival and Corrected Survival in Patients with Advanced Prostatic Cancer: Results from a Randomized Study Comprising 150 Patients Treated with Orchiectomy or Estrogens

In a population-based randomized study comparing 150 patients with advanced prostatic cancer treated with orchiectomy or estrogen, some possible prognostic factors were analyzed. The observation period was 78 to 114 months. M category, T category, tumor grade, performance status, pain, prostatic acid phosphatase, sedimentation rate, hemoglobin and serum creatinine level were all statistically significantly related to the interval to progression and to disease-specific death on univariate analyses. Variables that were statistically significant on multivariate analyses were M category, T category, sedimentation rate and patient age. The sedimentation rate predicted the intervals to progression and to disease-specific death, with the relative hazard and 95% confidence interval for the latter end point being 1.018 (range 1.010 to 1.027) for each millimeter increase in sedimentation rate per hour. An analysis that was stratified according to the extent of the disease as measured on a bone scan showed that the sedimentation rate was the only prognostic factor of statistical significance with an estimate of relative hazard of 1.52 if the sedimentation rate was elevated 20mm. per hour. Progression-free survival but not disease-specific survival was statistically significantly better in the estrogen group (relative hazard 0.47), as assessed by multivariate analysis in which all variables were taken into account.

The Risk of Dying of Prostate Cancer in Patients with Clinically Localized Disease

From 1966 to 1979, 360 patients with clinical stages A2, B and Cl prostate cancer underwent staging pelvic lymphadenectomy, and completed a course of combined interstitial radioactive gold seeds and external beam radiotherapy. All patients had a normal serum prostatic acid phosphatase level and a bone scan negative for metastases. All patients were followed until death or for a mean of 7.3 years (range 1.2 to 18.25 years) for those alive at analysis. To determine the risk of dying of prostate cancer we reviewed the records of the 142 patients (39%) who died. At analysis 21% of the patients had died of prostate cancer and 17% of other known causes. The cause of death could not be determined in 4 patients (1%). Cardiovascular disease accounted for a fifth of all deaths.The actuarial risk of death of prostate cancer for all patients was 8 ± 3% (± 2 standard errors) at 5 years and 30 ± 7% at 10 years. The risk of death of all causes was 16 ± 4% at 5 years and 46 ± 7% at 10 years. An increased risk of cancer death was associated with established risk factors, including advanced local disease, poorly differentiated histology, pelvic nodal metastases and distant recurrence. We also noted a substantial risk of cancer death in patients who had local tumor recurrence.While previous studies have reported a relatively low incidence of cancer deaths (4 to 17%) in patients initially diagnosed with localized disease, our data suggest that prostate cancer is the major cause of mortality in such patients. Aggressive curative therapy, regardless of treatment modality, should be considered for localized prostate cancer in men with a life expectancy of 10 or more years.

Multiple marker evaluation in prostatic cancer with prostatic acid phosphatase, γ-seminoprotein and prostate-specific antigen

Serum prostatic acid phosphatase (PAP), gamma-seminoprotein (gamma-Sm), and prostate-specific antigen (PA) levels were measured in 63 untreated patients with prostatic cancer. The sensitivities of PAP, gamma-Sm, and PA as markers of malignancy were 68%, 83%, and 77%, respectively. The latter two markers were more sensitive than PAP, especially in stage B disease. The specificities of PAP, gamma-Sm, and PA were 95%, 93%, and 93%, respectively. Patients with multiple positive markers were very likely to have prostatic cancer. In reactivation of the disease, positive rates for gamma-Sm and PA were higher than for PAP, indicating that the former two markers are more reliable for monitoring prostatic cancer.

Elevated prostate markers in metastatic small cell carcinoma of unknown primary

Numerous ectopic hormones and markers have been described in small cell carcinoma of the lung as well as in extrapulmonary small cell carcinomas. The authors report a case of a patient with metastatic small cell carcinoma of unknown primary who had very high prostatic acid phosphatase (PAP) and prostatic specific antigen (PSA) levels. Results of multiple prostate examinations, as well as blind biopsies, were normal. His course was significantly longer than that of the usual patient with extensive small cell carcinoma. At autopsy the prostate showed only mild benign prostatic hypertrophy. There are no previous reports in the literature of abnormal prostate markers in small cell carcinomas. Physicians should be aware of the increasing complexity and the unusual biologic markers associated with neuroendocrine carcinomas. In some of these cases, the tumors ability to produce an ectopic product may portend an improved prognosis.

Prostate irradiation does not affect the serum prostatic acid phosphatase level

Twenty-nine consecutive patients with localized prostatic carcinoma were studied prospectively to assess the effect of radical pelvic irradiation on the serum prostatic acid phosphatase level (SPAPL). The doses of radiation given ranged from 64.00 to 66.00 Gy. SPAPLs were taken before, during and shortly after their treatment. No significant individual variations in SPAPLs were found. When patients with prostatic carcinoma show rises in serum prostatic acid phosphatase during or after pelvic irradiation, these are unlikely to be due to their treatment and occult pelvic nodal or bony disease should be considered.

血清γ-seminoprotein と prostate-specific antigen 測定値の相関性についての臨床的検討

Serum levels of prostatic acid phosphatase (PAP), gamma-seminoprotein (gamma-Sm) and prostate-specific antigen (PSA) were determined simultaneously in 57 patients with benign prostatic hyperplasia (BPH) and in 50 untreated patients with prostatic cancer (adenocarcinoma, N = 47 and non-adenocarcinoma, N = 3). The correlations between the serum levels of gamma-Sm and PSA in these patients were assessed by linear regression analysis. Some fundamental studies were added for explaining the causes of discrepancy between the serum levels of gamma-Sm and PSA. All of BPH group underwent transurethral resection of the prostate (TURP) and the sera were obtained for measurements before, immediately after and 18 hours after TURP. The gamma-Sm correlated well with the PSA in the sera obtained before (r = 0.76) and 18 hours after (r = 0.73) TURP. However, there was no correlation (r = 0.26) between them in the sera obtained immediately after TURP. In 47 untreated patients with adenocarcinoma of the prostate, no significant correlation (r = 0.19) between serum levels of gamma-Sm and PSA was observed, although there was correlation (r = 0.51) between those of PAP and PSA. When these patients were classified into two groups, M0 (stage A-C; N = 26) and M1 (stage D; N = 21), however, the serum gamma-Sm correlated with the serum PSA in M0 group (r = 0.57), but didn't in M1 group (r = 0.11). Furthermore, the differences in the means of PAP (p less than 0.05) and PSA (p less than 0.001) between M0 group and M1 group were statistically significant, although the serum gamma-Sm failed to distinguish M0 from M1. The anti-PSA antibody of "PSA Kit" reacted against the standard gamma-Sm adopted from "gamma-Sm Kit". Surprisingly, the anti-gamma-Sm antibody of "gamma-Sm Kit" also reacted against the standard PSA adopted from "PSA Kit". The gamma-Sm and PSA apparently cross-reacted each other. The quantitative analyses with serial dilution of the sera were done by using each assay in 3 patients whose serum levels of gamma-Sm were markedly different from those of PSA. The dilution curve for PAP appeared to be rectilineal, and that for PSA also appeared to be approximately rectilineal. However, the gamma-Sm assay failed to be proportional. In conclusion, the correlation between serum levels of gamma-Sm and PSA was absent in certain circumstances, when the true values of them were expected to be much higher than those determined.(ABSTRACT TRUNCATED AT 400 WORDS)

Prostate-Specific Antigen in the Follow-Up of Prostatic Adenocarcinoma Treated with External Beam Radiation

Prostate-specific antigen (PSA) has been shown to be a more sensitive tumor marker than prostatic acid phosphatase (PAP) in prostatic adenocarcinoma: PSA was positive in 54 of our 117 patients (46%) and PAP was positive in 24 (21%). In order to compare the usefulness of these markers during and after radiotherapy serum samples from 24 patients treated with external beam irradiation were analyzed. PAP was only slightly positive in 1 patient (4%) after radiotherapy. His PSA level was highly elevated and he died of progressive disease. In the other 23 patients the cancer was in local control. However, the serum PSA level remained positive in 5 of these patients indicating vital cancer cells may still have been present. An alternative possibility is that metaplastic prostatic cells which secrete PSA were left after radiotherapy, as has been shown to be the case in prostatic hyperplasia. Before radiotherapy increased PSA levels were measured in 3 patients. In 2 of them the level declined to normal within 6 months after radiotherapy. The PAP levels were normal. It is concluded that PSA (positive in 25% of patients after radiotherapy) might be more sensitive than PAP (positive in 4%) in monitoring the effect of radiotherapy in prostatic cancer patients.

Reconstituted basement membrane promotes morphological and functional differentiation of primary human prostatic epithelial cells

Prostatic epithelial cells undergo rapid proliferation and lose their ability to synthesize and secrete prostate-specific antigen (PSA) and prostatic acid phosphatase (PAP) under standard tissue culture conditions. Herein, we compared the morphology, growth, secretory activity, and intermediate filament expression of human prostatic epithelial cells cultured on either standard tissue culture plastic or reconstituted basement membrane. Epithelial cells grown on plastic exhibited a 10-fold increase in proliferation and a higher percentage of cells in the S-phase of the cell cycle compared to cells cultured on basement membrane. However, cells grown on basement membrane secreted markedly higher levels of PSA and PAP. The basement membrane-induced enhancement of secretory activity was potentiated by dihydrotestosterone (DHT) and prostate stromal cell conditioned medium. Morphological studies showed that cells plated on basement membrane formed organoid-like clusters and maintained several aspects of differentiated epithelium including abundant secretory vesicles, microvilli, and desmosomes with associated cytoskeletal elements. Cultivation of epithelial cells on basement membrane components also suppressed the expression of vimentin, a mesenchymal intermediate filament polypeptide. However, cytokeratin expression was abnormal in cells grown on either surface. These results indicate that the differentiated properties of prostatic epithelial cells are promoted by cultivation on reconstituted basement membrane in the presence of DHT and stromal cell conditioned medium.

Prostate irradiation does not affect the serum prostatic acid phosphatase level

<h2>Abstract</h2> Twenty-nine consecutive patients with localized prostatic carcinoma were studied prospectively to assess the effect of radical pelvic irradiation on the serum prostatic acid phosphatase level (SPAPL). The doses of radiation given ranged from 64.00 to 66.00 Gy. SPAPLs were taken before, during and shortly after their treatment. No significant individual variations in SPAPLs were found. When patients with prostatic carcinoma show rises in serum prostatic acid phosphatase during or after pelvic irradiation, these are unlikely to be due to their treatment and occult pelvic nodal or bony disease should be considered.

Immunohistochemical prostatic acid phosphatase level as a prognostic factor of prostatic carcinoma

To determine whether prostatic acid phosphatase (PAP) immunoreactivity in prostatic adenocarcinoma is a reliable prognostic factor, the PAP immunohistochemical distribution has been examined in 78 prostatic carcinoma cases. The intensity of PAP immunostaining was graded from 0 to 2, and the scores of the primary and the secondary staining patterns were added to assess the extent of the PAP expression in needle biopsy specimens. As a result, a higher cancer-specific survival rate was observed in patients showing a greater PAP immunostaining (P less than 0.01). Further, a multivariate analysis was made of possible prognostic factors (age, stage, Gleason score, serum PAP, PAP-immunostaining score, and the initial treatment) to estimate the extent of their impact on cancer-specific survival. Results have confirmed that the difference in PAP immunoreactivity is an excellent, independent prognostic factor for prostatic carcinoma.

The role of prostatic specific antigen in monitoring prostatic cancer and its prognostic importance

Serum prostatic specific antigen (PA) and prostatic acid phosphatase (PAP) levels were measured in 113 untreated patients with prostatic cancer and in 137 patients with benign prostatic hypertrophy (BPH). Of the 113 cancer patients, 81% and 69%, respectively, were detectable by means of PA or PAP assay alone. PA was a more sensitive indicator, than PAP in all stages, especially localized disease (stages A, B and C). Using the BPH group as a negative control, specificities of PA and PAP were 81% and 94% respectively. In another group of 68 patients with BPH whose blood samples were taken immediately after prostatic manipulation, both PA and PAP levels were elevated significantly. In 87 of the 113 cancer patients the two markers were serially determined, and 22 patients presented disease progression. Concerning the sensitivity within 6 months before progression, PA appears to be more reliable than PAP in early detection of disease progression. According to Kaplan-Meier projections, the patients with normal pretreatment PA levels had significantly longer intervals to progression than did those with moderate to marked PA elevation (more than 100 ng/ml) (P less than 0.05). This study shows that PA is more reliable than PAP for detection and monitoring of prostatic cancer. Pretreatment PA levels appear to be of a high prognostic value for time to progression, irrespective of stage and treatment regimen.

Serum Acid Phosphatase in Patients with Localised Prostatic Cancer, Benign Prostatic Hyperplasia or Normal Prostates

Serum acid phosphatase levels were determined in 247 men with surgically confirmed intracapsular prostatic cancer (30 patients), benign prostatic hyperplasia (BPH) (114 patients) or palpably normal prostates (103 men). Both radioimmunoassay (245 cases) and an enzymatic method (218 cases) were used. Using radioimmunoassay, the mean serum prostatic acid phosphatase (PAP) level was significantly higher in patients with BPH than in patients with intracapsular cancer or men with normal prostates. The weight of hyperplastic tissue removed during operation in the BPH group correlated closely with PAP concentrations. Age or the presence (or absence) of an indwelling catheter had no effect on PAP concentration. Using the enzymatic method, the highest levels of acid phosphatase were also detected in patients with BPH but the difference was less marked. It was concluded that intracapsular cancer does not elevate serum acid phosphatase levels as determined by radioimmunoassay or an enzymatic method. BPH alone leads to significant rises in PAP concentrations. The degree of BPH correlates with PAP levels.