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Relationship between prostatic acid phosphatase and prostate-specific antigen serum levels and prostatic volume in benign prostate hyperplasia. Pitfall on tumor markers assessment in primary prostatic cancer?

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.

Acid Phosphatase

Changes in prostate-specific antigen and prostatic acid phosphatase concentration following prostatic examination in benign prostatic hypertrophy and prostate cancer patients.

The authors measured serum prostate-specific antigen (PSA) and prostatic acid phosphatase concentration in histologically positive prostate hyperplastic and carcinomatous patients before, and 30-60 min and 24 h after prostate manipulation (rectal digital examination, cystoscopy and perineal punch biopsy). After rectal examination, PSA, and after other interventions, both markers changed significantly, although in different points of time and to a different extent. The authors call the attention to the importance of the point of time of the examination. Examination following prostate manipulation may result in wrong diagnosis or in erroneous therapeutic consequences in the follow-up period.

Acid Phosphatase

Evaluation of prostate-specific antigen and prostatic acid phosphatase in untreated prostatic carcinoma and benign prostatic hyperplasia.

Prostate specific acid phosphatase (PAP) (Abbott, solid-phase enzyme immunoassay) and prostate specific antigen (PSA) (Hybritech, immunoradiometric assay) were determined in 162 newly diagnosed prostatic carcinoma patients, 187 patients with benign prostatic hyperplasia (BPH) and 127 controls. The upper limit of normal in controls for PAP was 2.2 micrograms/l and for PSA 5.0 micrograms/l. In the BPH group PAP was raised in 21%, for PSA in 41%. When the cut-off level of PSA was raised to 10.0 micrograms/l, 20% of BPH patients had an increased level. PSA was superior to PAP for the detection of prostatic cancer in all stages. Of the 162 patients with prostatic carcinoma, 88 had localised diseases and 74 had metastatic spread. PSA and PAP levels increased with each advancing clinical stage. PAP was elevated in 35% of the patients with cancer confined to the prostate. PSA in 69%. (PSA level 10.0 micrograms/l: 57%). In those patients with metastatic spread PAP was elevated in 77% compared with 96% for PSA. (PSA level 10.0 micrograms/l: 92%). The combined use of PSA and PAP does not give a greater accuracy in the screening of prostate cancer when compared with the sole use of PSA. PAP was elevated in only 4 patients when PSA was normal. In the BPH group there was no proven effect of micturition, frequency or residual urine on the SPA level. However, in this group infection may cause a rise in the PSA level.

Acid Phosphatase

Volume of normal prostate, of prostate cancer, and of benign prostatic hyperplasia: are correlations with prostate specific antigen clinically useful?

This retrospective study correlated prostate volume, determined by transrectal ultrasonography, with serum prostate specific antigen (PSA), by Deming regression analysis, in patients with confirmed benign prostatic hyperplasia (BPH) and patients with non-metastatic (M0) or metastatic (M1) prostate cancer. In BPH, a highly significant correlation was found between log10[PSA] and prostate volume. When this PSA/volume regression pattern for BPH was used as a reference standard, all 17 patients with M1 prostate cancer and 83% of the 23 patients with M0 disease were discriminated from BPH.

Aged

Characterization of prostate cancer, benign prostatic hyperplasia and normal prostates using transrectal 31phosphorus magnetic resonance spectroscopy: a preliminary report.

We assessed the ability of 31phosphorus (31P) transrectal magnetic resonance spectroscopy to characterize normal human prostates as well as prostates with benign and malignant neoplasms. With a transrectal probe that we devised for surface coil spectroscopy we studied 15 individuals with normal (5), benign hyperplastic (4) and malignant (6) prostates. Digital rectal examination, transrectal ultrasonography and magnetic resonance imaging were used to aid in accurate positioning of the transrectal probe against the region of interest within the prostate. The major findings of the in vivo studies were that normal prostates had phosphocreatine-to-adenosine triphosphate (ATP) ratios of 1.2 +/- 0.2, phosphomonoester-to-beta-ATP ratios of 1.1 +/- 0.1 and phosphomonoester-to-phosphocreatine ratios of 0.9 +/- 0.1. Malignant prostates had phosphocreatine-to-beta-ATP ratios that were lower (0.7 +/- 0.1) than those of normal prostates (p less than 0.02) or prostates with benign hyperplasia (1.1 +/- 0.2, p less than 0.01). Malignant prostates had phosphomonoester-to-beta-ATP ratios (1.8 +/- 0.2) that were higher than that of normal prostates (p less than 0.02). Using the phosphomonoester-to-phosphocreatine ratio, it was possible to differentiate metabolically malignant (2.7 +/- 0.3) from normal prostates (p less than 0.001), with no overlap of individual ratios. The mean phosphomonoester-to-phosphocreatine ratio (1.5 +/- 0.5) of prostates with benign hyperplasia was midway between the normal and malignant ratios, and there was overlap between individual phosphomonoester-to-phosphocreatine ratios of benign prostatic hyperplasia glands with that of normal and malignant glands. To verify the in vivo results, we performed high resolution magnetic resonance spectroscopy on perchloric acid extracts of benign prostatic hyperplasia tissue obtained at operation and on a human prostatic cancer cell line DU145. The extract results confirmed the differences in metabolite ratios observed in vivo. We conclude that transrectal 31P magnetic resonance spectroscopy can characterize metabolic differences between the normal and malignant prostate.

Adult

Prostate specific antigen density: a means of distinguishing benign prostatic hypertrophy and prostate cancer.

Isolated prostate specific antigen (PSA) determinations in asymptomatic individuals have not demonstrated sufficient sensitivity and specificity to be useful in the routine evaluation of prostate disease. To enhance the accuracy of serum PSA we have used a quotient of serum PSA and prostate volume, which we refer to as prostate specific antigen density (PSAD). Prostate volume in this study was calculated from magnetic resonance imaging determinations of benign prostatic hypertrophy (BPH) or from the dimensions of the surgical specimen of cancer using the formula, length x width x depth x 0.5 = volume. A total of 61 patients with prostatic disease clinically confined to the prostate glands (41 with prostate cancer undergoing radical prostatectomy and 20 with BPH) was evaluated. The mean PSAD for prostate cancer was 0.581 while that for BPH was 0.044 (p less than 0.002). No patient with BPH had a PSAD of greater than 0.117 and only 1 patient had a density of 0.1 or greater. Of 34 patients with a PSAD of 0.1 or greater 33 had prostate cancer. Only 2 of the 41 prostate cancer patients and 14 of the BPH patients had a PSAD of 0.05 or less. There were 11 patients with a PSAD of greater than 0.05 and less than 0.1, including 6 with prostate cancer (1 with P0 disease) and 5 with BPH. Of the 6 prostate cancer patients 5 had a PSA of 4.0 or less and among the 5 patients with BPH 4 had a serum PSA of greater than 4.0 and 1 had a PSA of greater than 10. These results suggest that PSAD may be useful in distinguishing BPH and prostate cancer.

Antigens, Neoplasm

Pre-analytical and biological variability of prostatic acid phosphatase and prostate-specific antigen in serum from patients with prostatic pathology.

We determined the pre-analytical and biological variation of prostatic acid phosphatase and prostate-specific antigen in the same patient samples. Prostatic acid phosphatase and prostate-specific antigen were both stable when stored for at least 3 weeks with acidification (acetate buffer) or without acidification, except for prostate-specific antigen in samples stored unacidified at 4 degrees C. A significant elevation of prostate-specific antigen was noted in four patients with benign prostatic hyperplasia between 1/2 and 6 hours after prostatic massage. No significant effect was shown of changes in the glomerular filtration rate on prostate-specific antigen concentration, in spite of its low molecular mass. The estimate of within-subject biological variation showed a coefficient of variation of 33.8% for prostatic acid phosphatase and 14% for prostate-specific antigen. Desirable analytical imprecisions based on these findings were about 17% for prostatic acid phosphatase and 7% for prostate-specific antigen, these goals being achieved in practice for marker values higher than or equal to the upper reference limit.

Acid Phosphatase

Measurement of prostate-specific antigen and prostatic acid phosphatase concentrations in serum before and 1-42 days after transurethral resection of the prostate and orchidectomy.

Preoperative intra-individual variation for determinations of prostate-specific antigen and prostatic acid phosphatase concentrations, 15-30% in 92 patients with benign prostatic hyperplasia, limits the diagnostic usefulness of both tumor markers. In benign prostatic hyperplasia (214 patients), concentrations of these tumor markers increased in the initial postoperative period. Prostatic acid phosphatase concentration then decreased by the third postoperative day. Prostate-specific antigen concentration remained above normal in the first postoperative week but had decreased by 42 days. In prostatic carcinoma (46 patients), the concentrations of these tumor markers did not increase postoperatively. During the first week, the concentrations of prostatic acid phosphatase began to fall, but prostate-specific antigen showed a decrease only at 42 days. After orchidectomy (11 patients), the concentrations of both markers had decreased by five days. Concentrations of prostate-specific antigen but not of prostatic acid phosphatase were significantly increased in patients with metastases at 42 days postoperatively. When the concentration of tumor marker did decrease, the magnitude of change was greater for prostatic acid phosphatase than for prostate-specific antigen. These changes were accentuated after an orchidectomy.

Acid Phosphatase

Estimation of prostatic growth using serial prostate-specific antigen measurements in men with and without prostate disease.

Prostate growth curves were estimated from serial prostate-specific antigen (PSA) measurements on frozen sera in three groups of men: (a) 16 men with no prostatic disease by urological history and examination; (b) 20 men with a histological diagnosis of benign prostatic hyperplasia (BPH) who had undergone simple prostatectomy; and (c) 18 men with a histological diagnosis of prostate cancer. The median number of repeated PSA measurements over an 8- to 26-yr period prior to histological diagnosis or exclusion of prostate disease was eight and 11 for noncancer and cancer subjects, respectively. Predicted rates of change in PSA (PSA velocity) were linear and curvilinear for control and BPH subjects, respectively. Subjects with cancer demonstrated both a linear and an exponential phase of PSA velocity. Based on time to double PSA, we estimated the epithelial doubling time for men without prostate disease to range from 54 +/- 13 yr at age 40 to 84 +/- 13 yr at age 70. For men with BPH, doubling times ranged from 2 +/- 13 yr at age 40 to 17 +/- 5 yr at age 85. Subjects with local/regional and advanced/metastatic cancer had similar PSA doubling times of 2.4 +/- 0.6 yr and 1.8 +/- 0.2 yr, respectively. These data are consistent with what is known about prostatic growth with age in men without prostate disease and BPH, and the kinetics of prostate cancer growth. Estimates of prostatic growth rate from changes in PSA may be useful clinically in management of men with prostate disease.

Aged

Active principle of swine prostate extract: II. Effect of a peptide isolated from swine prostate extract on rat prostate.

Previously, we purified a substance from swine prostate extract (PE) that had been reported to have therapeutic effect on benign prostatic hypertrophy. The purified substance (PPE) suppressed 3H-testosterone uptake into the prostate in castrated rats. The present study was carried out to examine the effect of PPE on the weight of accessory sexual organs including the prostate and biochemical parameters in the prostate of normal and/or castrated and testosterone-treated rats. 1) In normal rats, the p.o. administration of PPE daily for a total of 30 days did not affect the prostate weight, but reduced the citric acid content in the prostate. The treatment had little or no influence tissue O2 uptake, aconitase activity or isocitrate dehydrogenase activity in the prostate. 2) In castrated and testosterone-treated rats, the p.o. treatment with PPE for 15 or 30 days reduced the weight of the prostate as well as the total citric acid, DNA and RNA contents in prostatic tissue. However, these biochemical parameters per tissue weight were not obviously affected except for the citric acid content. These findings suggest that PPE is one of the active principals of PE for the therapeutic efficiency on benign prostatic hypertrophy, probably due to its suppressive effect on excessive uptake of androgen by the prostate.

Aconitate Hydratase

Prostate-specific antigen levels in 1695 men without evidence of prostate cancer. Findings of the American Cancer Society National Prostate Cancer Detection Project.

The American Cancer Society National Prostate Cancer Detection Project is a prospective, multidisciplinary, and multicenter trial to assess the potential for early detection of prostate cancer by transrectal ultrasonography (TRUS), digital rectal examination (DRE), and serum prostate-specific antigen assay (PSA). By November 1990, 2805 men between the ages of 55 and 70 years with no known signs or symptoms of prostate cancer were enrolled in the study, which is planned to run for 5 years. Annual TRUS, DRE, and PSA tests were done on these subjects, and biopsies were recommended for suspicious lesions when detected. To study the performance of PSA testing in presumed normal subjects, all men were eliminated who had (1) prostate cancer detected on their initial examinations and proven by biopsy or (2) cancer detected during the year or subsequent examinations. Additionally, all men with TRUS or DRE findings that were interpreted as suspicious for cancer but who are being followed and have not yet had biopsies done were removed from this series. This left a unique, extensively screened group of 1695 men who were free of prostate cancer, as far as could be determined. Analyses of the PSA levels in this large population in the appropriate age range for increasing risk of prostate cancer revealed several important findings. First, there was a direct relationship between serum PSA levels and estimated prostate volume for both the currently available monoclonal and polyclonal PSA assays. Individuals with benign prostatic hyperplasia and larger gland volume have a higher normal limit of PSA than men with normal gland volume. Second, analyses showed no relationship between age and PSA levels or between symptoms of prostatism and PSA levels independent of gland enlargement. It was concluded that volume-adjusted upper limits of normal PSA can be determined for different levels of specificity desired. This information may be applicable to the use of PSA in men not already suspected of having prostate cancer and may increase its effectiveness as a tool for early detection.

Age Factors

Prostate and bone fibroblasts induce human prostate cancer growth in vivo: implications for bidirectional tumor-stromal cell interaction in prostate carcinoma growth and metastasis.

Prostate cancer selectively metastasizes to the axial skeleton to produce osteoblastic lesions, which suggests that bidirectional paracrine interactions exist between prostate cancer and bone cells. To evaluate the role of tumor-stromal cell interaction and stromal-specific growth factors in prostate cancer growth and dissemination, we coinoculated nontumorigenic human prostate cancer cells (LNCaP) and various tissue-specific fibroblasts subcutaneously in athymic mice. LNCaP tumors were induced most consistently by human bone fibroblasts (62%), followed by two prostate fibroblast cell lines (31% and 17%), but not by lung, kidney, or embryonic 3T3 fibroblasts. Carcinomas formed preferentially in male hosts, demonstrating in vivo androgen sensitivity. Immunohistochemical and biochemical techniques confirmed the human prostate component of these tumors and were paralleled by elevations in serum prostate specific antigen. In vitro mitogenic assays revealed a two-to three-fold bidirectional stimulation between LNCaP and bone or prostate fibroblast conditioned media, but not lung, kidney, or 3T3 fibroblast conditioned media. A novel method developed to deliver concentrated bone or prostate fibroblast conditioned media in vivo using a slowly absorbed matrix (gelfoam) also induced tumor formation, emphasizing the importance of fibroblast growth factors in LNCaP tumor formation. Northern analysis identified the stromal compartment as the primary source of extracellular matrix (collagen, fibronectin), while only LNCaP cells expressed transforming growth factor alpha. Although LNCaP and stromal cells express basic fibroblast growth factor (bFGF), the bidirectional paracrine-mediated mitogenic activity between these cells is not inhibited by anti-bFGF antibodies, suggesting that other undefined growth factors may be involved in stimulating LNCaP growth. These observations illustrate the importance of stromal-epithelial interaction in prostate tumor growth and suggest that extracellular matrix and paracrine-mediated growth factors play a role in prostate cancer growth and metastasis.

Androgens

[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

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

[Quantitative analyses of alpha-adrenoceptors in human prostatic capsule, adenoma and urethra--a comparison between normal prostate and hypertrophied prostate].

The adrenergic alpha-1 and -2 receptors in the three layers of the prostate (capsule, adenoma and urethra) were measured in humans with or without benign prostatic hypertrophy to examine the differences between the hypertrophied and non-hypertrophied (normal) prostate. Both alpha-1 and -2 receptors were found to exist in similar amounts in prostatic adenoma of both hypertrophied and normal prostate groups. In the prostatic capsule and urethra of both groups alpha-1 receptors were more abundant than alpha-2 receptors. Both alpha-1 and -2 receptors in all three prostatic layers were found to be increased significantly in hypertrophied group compared to normal group. Further more the increases in alpha-1 and -2 receptors of hypertrophied group were most remarkable in prostatic adenoma. These results seems to demonstrate that not only alpha-1 but also alpha-2 receptors play some important roles in benign prostatic hypertrophy.

Adenoma

Correlation between prostate-specific antigen and prostate volume, evaluated by transrectal ultrasonography: usefulness in diagnosis of prostate cancer.

The authors calculated the volume of the prostate by transrectal ultrasonography and evaluated prostate-specific antigen (PSA) in 108 patients with benign prostatic disease or with clinically suspected carcinoma and in 35 normal subjects. In each case the PSA value was related to the corresponding gland volume (V), which gives a PSA/V index. 32 patients underwent transurethral resection, 23 underwent open prostatectomy and biopsy was performed in 53. Histological examination revealed benign prostatic hyperplasia in 63, prostatitis in 12 and carcinoma in 33. In normal subjects and in those with benign prostatic diseases, the mean PSA/V index was 0.090 and 0.099, respectively. In patients with prostatic carcinoma the ratio was 1.73. The authors propose that this ratio be used, as an alternative to the absolute value of PSA, to differentiate patients with benign and malignant diseases of the prostate.

Aged

Influence of prostatic disease and prostatic manipulations on the concentration of prostate-specific antigen.

We examined the influence of different factors [benign prostatic hyperplasia (BPH), prostatic carcinoma (PCA), organ volume, weight of resected tissue, transurethral catheter] on the serum prostate-specific antigen (PSA) levels in 253 patients with BPH (n = 138; 54%) and PCA (n = 115; 46%). Only in 57.2% of the BPH patients, PSA values were < 4 ng/ml, in 74.6% < 7 ng/ml. In 108 patients with BPH, a transurethral prostatectomy was performed. PSA values correlated significantly with the sonographically determined prostatic volumes and less precisely with the weight of the resected tissue. The PSA concentration per milliliter of prostatic volume was 0.12 ng/ml, per gram of resected tissue it was 0.21 ng/ml. An incidental PCA was found in 12/108 patients (11%). The PSA values were identical with those of the total collective in regard to volume and tissue weight. In 11 patients, we examined possible alterations of the PSA values before and until 24 h after prostatic massage. Only insignificant alterations were seen, a massive increase was not found in any patient. Searching for an absolutely valid 'normal value' appears hardly appropriate. However, the usefulness of PSA is increased when the sonographically determined prostatic volume is included. A rectal examination of the prostate has no influence on the PSA value.

Aged

Prostate specific antigen and prostatitis. I. Effect of prostatitis on serum PSA in the human and nonhuman primate.

Prostate specific antigen (PSA) has become a mainstay in the diagnosis and management of patients with prostate cancer. We have found, as have others, that it may be elevated in patients with prostatic inflammation. Ten patients had clinical evidence of prostatitis and elevated PSA levels. Six of these had persistently elevated levels after antibiotic treatment. After transrectal ultrasonography and biopsy, two had findings of adenocarcinoma, and the rest had a pathologic diagnosis of acute or chronic prostatitis. We studied this process in an experimental model of prostatitis using a nonhuman primate. We infected six cynomolgus monkeys and followed their PSA levels until resolution of the infection. The PSA peaked between 5 and 7 days after inoculation and gradually returned to baseline in 8 weeks. The dramatically elevated serum PSA levels in bacterial prostatitis can cause confusion in the diagnosis of prostatic carcinoma.

Adult