Characterization and measurement of the androgen receptor in human benign prostatic hyperplasia and prostatic hyperplasia and prostatic carcinoma.
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Our investigation of normal, hyperplastic, and neoplastic prostatic tissue during the past 2 1/2 years has produced several findings which have been published or accepted for publication. (a) Cells from hamster prostates with intense histochemically demonstrable acid phosphatase activity (HDAP) after fixation with formaldehyde which we believe to be epithelial cells can be obtained in 97.2% +/- 0.8% purity by velocity sedimentation in a previously described isokinetic density gradient; (b) similarly, cells with HDAP, many of which contain lipofuscin granules, can be obtained as 81.0% +/- 12.2% of nucleated cells from hyperplastic human prostates and as 86.4% +/- 9.4% of nucleated cells from human prostatic carcinomas; (c) more cells were obtained from human hyperplastic prostates and prostates with prostatic carcinoma per gram of tissue with the aid of Pronase than were obtained with trypsin, collagenase, or mechanical methods; (d) more cells per gram of tissue were obtained from surgically removed prostates than from prostates obtained at even very rapid autopsies, and a much larger proportion of the cells from surgically removed prostates were viable as assessed both by dye exclusion and by plating efficiency; (e) none of several substrates and inhibitors which we tested were highly specific for acid phosphatase from purified prostatic epithelial cells compared with several other kinds of purified human cells; and (f) purified hamster prostatic epithelial cells incorporate large amounts of tritiated thymidine in 72-hour cultures.
In an attempt to identify an indicator(s) specifically associated with prostatic cancer prostatic fluid was collected by rectal massage from patients with prostatic cancer, prostatitis, benign prostatic hyperplasia and from those without recognized prostatic lesions in order to measure various immunoproteins. The proteins examined were IgG, IgA, IgM, complements C3 and C4, and transferrin. Prostatic fluid samples were subjected first to immunoelectrophoresis. Distinct differences in C3, C4 and transferrin concentrations were noted between patients with prostatic cancer and other patients. These proteins were stained heavily in the electrophoresis gels of fluid from cancer patients but were either missing or lightly stained in all other groups. These qualitative determinations were replaced subsequently by a quantitative measurement using the radial immunodiffusion technique. Results of the latter study confirmed the aforementioned observations and indicated that the levels of C3, C4 and transferrin in the prostatic fluid of cancer patients were elevated significantly when compared to all other patient groups. These observations indicate that the measurement of complements C3 and C4, and transferrin in the prostatic fluid may assist in the identification of patients with a high risk of prostatic cancer.
RATIONALE: A range of surgical options is available for the treatment of benign prostatic hyperplasia (BPH), including holmium laser enucleation of the prostate (HoLEP). The evidence is unclear regarding differences in functional, perioperative, and morbidity outcomes between these modalities. OBJECTIVES: To assess the effects of holmium laser enucleation of the prostate compared with other surgical treatments for lower urinary tract symptoms in men with benign prostatic hyperplasia. SEARCH METHODS: We searched multiple databases (including MEDLINE, Embase, CENTRAL, Web of Science, LILACS, and the International HTA database), trial registries, and conference abstracts through April 08, 2026. ELIGIBILITY CRITERIA: We only included randomized trials of men over 40 years of age with a prostate volume of at least 20 mL (assessed by digital rectal examination, ultrasound, or conventional imaging) who exhibited lower urinary tract symptoms (LUTS) defined by an International Prostate Symptom Score (IPSS) of eight or greater undergoing surgical interventions for BPH. OUTCOMES: The critical outcomes measured were the urologic symptoms score, the quality-of-life score, and major adverse events. The important outcomes measured were: re-treatment, erectile function, ejaculatory function, transfusions, acute urinary retention, indwelling urinary catheter duration, and hospital stay duration. RISK OF BIAS: We used the Cochrane risk of bias tool (RoB 1) to assess for potential sources of bias on a study and outcome level basis. SYNTHESIS METHODS: We pooled outcome data using the random-effects model and performed meta-analyses using the Mantel-Haenszel method. We assessed statistical heterogeneity in the pooled data by visually inspecting forest plots and using the I2 statistic to quantify it. We used the GRADE framework to assess the certainty of evidence. INCLUDED STUDIES: We included 52 trials that included 6242 participants that compared HoLEP to other surgical interventions for benign prostatic hyperplasia. The median age of participants across the studies ranged from 65 to 74 years. The baseline prostate volume ranged from 30 cc to 142 cc. Baseline IPSS scores ranged from 19.6 to 28.6 (range 0-35). SYNTHESIS OF RESULTS: We prioritized comparing HoLEP with transurethral resection of the prostate (TURP) at short-term follow-up (up to 12 months), because TURP is the long-standing reference standard and the predominant comparator in randomized surgical trials. Findings for the four remaining comparisons (laser ablation, alternative energy source enucleation, other minimally invasive therapies, and simple prostatectomy), for long-term follow-up, and for all remaining outcomes are reported in full in the review. Compared to TURP, at short-term follow-up: Critical outcomes - HoLEP may result in little to no difference in short-term urologic symptom scores measured using the IPSS (range 0 to 35; lower values reflect fewer symptoms) (MD -0.67, 95% CI -1.20 to -0.14; I² = 93%; 14 studies, 1666 participants, low-certainty evidence). - HoLEP may result in little to no difference in short-term quality of life (range 0 to 6; lower values reflect better quality of life) (MD -0.04, 95% CI -0.23 to 0.15; I² = 73%; 6 studies, 876 participants, low-certainty evidence). - HoLEP may result in little to no difference in short-term major adverse events (RR 0.75, 95% CI 0.35 to 1.58; I² = 0%; 10 studies, 1147 participants, low-certainty evidence). Important outcomes - HoLEP likely results in little to no difference in re-treatment (RR 0.45, 95% CI 0.14 to 1.50; I² = 0%; 8 studies, 813 participants, moderate-certainty evidence). - HoLEP likely results in little to no difference in erectile function (MD -0.03, 95% CI -0.47 to 0.42; I² = 0%; 3 studies, 518 participants, moderate-certainty evidence). - Ejaculatory function: we did not find any data for this outcome. - HoLEP likely reduces the need for blood transfusion (RR 0.19, 95% CI 0.09 to 0.42; I² = 0%; 15 studies, 1755 participants, moderate-certainty evidence). AUTHORS' CONCLUSIONS: Compared with TURP, HoLEP may achieve similar relief of urologic symptoms, similar quality of life, and similar rates of major adverse events in the first 12 months after surgery, and probably similar re-treatment rates and erectile function. HoLEP likely reduces the need for blood transfusion; this is the only advantage of HoLEP that the randomized evidence, as summarized here, supports as clinically important. There was insufficient evidence to assess outcomes in the subset of individuals with larger prostates or on anticoagulation. Future research should prioritize long-term trials reporting sexual function and urinary incontinence outcomes, recruit men with very large prostates (≥ 150 cc) or on anticoagulation therapy, and evaluate cost-effectiveness and training requirements. FUNDING: No external funding was received for this review. REGISTRATION: The protocol for this review was published in the Cochrane Database 2019 (https://doi.org/10.1002/14651858.CD013291).
Prostatic acid phosphatase from human seminal fluid was purified to homogeneity. The enzyme was characterized as to its purity, molecular weight and amino acid composition. Analytical isoelectric focusing of purified enzyme on polyacrylamide gels resolved the enzyme activity into eleven discrete bands, apparently due to various amounts of sialic acid associated with the glycoprotein. Antisera raised against the purified enzyme produced only one precipitan arc on immunoelectrophoresis. A double antibody radioimmune assay was developed and used to evaluate serum prostatic acid phosphatase in 226 patients without prostatic disease, in 186 patients with benign prostatic hyperplasia and in 93 patients with prostatic carcinoma. No statistical difference was noted in serum prostatic acid phosphatase between patients with benign prostatic hyperplasia and in those without prostatic disease Serum prostatic acid phosphatase was elevated in 94% of the patients with metastatic prostatic carcinoma. Significant elevations were also found in carcinoma patients without metastases.
To sum up the role of zinc in prostatic physiology and biochemistry: a) Zinc is found in normal prostate tissue in a greater concentration than in any other organ in the economy, ranging between 0.70 and 1 mgm/gm. of dry tissue. b) The concentration of prostate liquid and semen is greater than that in any other organic liquid. c) It appears that the prostate gland is a zinc storing organ (or deposit). d) The zinc concentration in prostatic tissue is directly proportional to the amount of alveolar tissue existing in the gland. e) It has been shown that the Zn concentration is greater in the nuclear sediment of the different subcellular fractions of the human prostate gland. f) The prostate gland seems to supply zinc to the human sperm and plays an important role in the metabolic activity of the spermatozoid. g) There seems to be a clear difference between the distribution and absorption of radioactive zinc in the different lobes of the prostate gland. h) Zinc also plays an important part in the enzymatic activity of the prostate gland and in the polymeric organization of the RNA and DNA and is vital for cell division. i) Prostatic Zn has a clear hormonal dependency.
Normal prostate glands from 6 men less than 30 years old and enucleated tissue of benign prostatic hyperplasia were analyzed by stereological methods. Studies on the relative volumetric amount of fibromuscular (stromal) and glandular areas of the gland reveal no statistically significant difference between the inner and outer parts of the normal prostate and between the inner part of the normal prostate and benign prostatic hyperplasia. However, in benign prostatic hyperplasia there is a significant increase in the volumetric amount of the fibromuscular tissue and a decrease in the glandular area compared to the outer part of the normal prostate and the whole normal prostate (sum of the inner and the outer parts). These stereological data are discussed with respect to the pathogenesis of benign prostatic hyperplasia.
Today, the transrectal fine-needle biopsy is firmly integrated in the establishment of the diagnosis of prostate carcinoma within the prophylactic examinations and as a check-up examination during the treatment of prostate carcinoma. Cytologically, the prostate carcinoma may be divided into four different degrees of malignancy: high-grade, medium-grade, low-differentiated and anaplastic carcinoma. Differential-diagnostically, chronic prostatitis may raise certain problems both clinically and cytologically. Electronmicroscopic examinations of samples taken by fine-needle biopsy are possible. Certain changes under anti-androgen treatment are examined at present. Under the contra-sexual treatment of the prostate carcinoma carrier there occur changes of the normal and carcinoma cells the extent of which permits conclusions as to the therapeutic hormone effect. This, in turn, results in consequences for the respective treatment. In 496 prostate carcinomata cytologically diagnosed since March 1970 the author was able to demonstrate that the 5 years' survival rate is determined by the cytological degree of differentiation. Whereas highly and medium-differentiated prostate carcinomata show an average 5 years' survival rate of 62.5 per cent, this amounts only to 33.9 per cent with the low-differentiated and anaplastic prostate carcinomata. The total 5 years' survival rate of all cytologically diagnosed carcinomata came up to 46.8 per cent. The 1-, 2-, 3-, 4- and 5 years' survival rate of all cytologically diagnosed prostate carcinoma carriers is almost in conformity with the values found by Esposti. The degree cytological differentiation in connection with the clinical stage clearly determines the clinical course with our patients.
Cytosol from human benign hyperplastic and carcinomatous prostatic tissue has been shown to contain a progestin receptor with a dissociation constant of approximately 10(-9) M. The receptor was measured using 3H-labeled R 5020 (17 alpha, 21-dimethyl-19-nor-4,9-pregnadiene-3,20-dione) as ligand. Progesterone, cyproterone acetate, and R 1881 (methyltrienolone) were efficient competitors to R 5020 for binding sites on the receptor whereas testosterone, 5 alpha--dihydrotestosterone, estradiol, cortisol, and several hydroxylated and saturated derivatives of progesterone did not compete. The [3H]R 2020-receptor-complex had a sedimentation coefficient of approximately 4 S, an isoelectric point of approximately 5, was heat-labile, and was destroyed by treatment with trypsin but not with deoxyribonuclease or ribonuclease. Seventeen of 21 patients with benign prostatic hyperplasia and three patients with prostatic carcinoma had 1 to 40 fmoles of specific R 5020-binding sites per mg of cytosol protein. One sample of normal prostatic tissue did not contain significant amounts of progesting receptor. Tissue specimens removed by transvesical adenoma enucleation displayed a larger number of specific R 5020-binding sites than electroresected specimens. The progestin receptor in hyperplastic prostate may be involved in the mechanism of the action of progestins used in the medical treatment of benign prostatic hyperplasia. Quantitation of progestin receptor in cancer of the prostate may form part of the basis of a predictive test program for endocrine therapy of prostatic malignancy.
We compared our radioimmunoassay with the standard enzyme assay for prostatic acid phosphatase in the diagnosis of prostatic cancer. Serum samples from 50 controls, 113 patients with prostatic cancer, 36 with benign prostatic hyperplasia, 83 with other cancers, 20 with gastrointestinal disorders and 28 with total prostatectomies were randomized and studied by radioimmunoassay and enzyme assay. When the upper limit was set at 8.0 ng per milliliter (mean + 4 S.D.) the radioimmunoassay diagnosed prostatic cancer in 33, 79, 71 and 92 per cent of the patients with Stage I, II, III and IV disease. In contrast, the enzyme assay detected elevations of enzyme in the serum of 12, 15, 29, and 60 per cent respectively. No false-positive results were detected by either assay in normal controls but the radioimmunoassay test was positive in two patients with benign prostatic hyperplasia, in one patient after total prostatectomy, in nine with other cancers and in one of the group with gastrointestinal disorders. In contrast to the enzyme assay, the radioimmunoassay distinguished over half the cases of intracapsular prostatic cancer.
"Prostatic acid phosphatase" is a term that has been used widely and ambiguously to refer to acid phosphatase, which 1) is elevated in the sera of patients with various diseases of the prostate, 2) is inhibited by one or more specific inhibitors, 3) attacks one or more specific substrates, 4) has certain unique antigenic properties, 5) is extracted from homogenates of prostate, and 6) is obtained from prostate secretions, etc. Most of the data adduced to justify this term is indirect. We have purified specific kinds of cells from prostates and other tissues. These purified cells have served as sources of enzymes known to be derived from particular kinds of cells. We studied several substrates and one inhibitor that have been claimed useful for the measurement of prostatic acid phosphatase. None of the substrates or inhibitors studied appeared to offer much "specificity," which would allow us to distinguish acid phosphatase activity from prostatic epithelial cells from acid phosphatase activities from several other kinds of purified cells.
Normal and benign hyperplastic prostatic tissue was studied by quantitative electron microscopic measurements. Quantitative morphological procedures provide values for volume, surface, number of tissue and cellular components within human prostatic tissue. When a comparison is made of the stereological data of the glandular cell of benign prostatic hyperplasia to that of the normal human prostate no statistically significant difference in the relative volumetric amount of the cell organelles is indicated. An attempt was made to characterize the fine structure of the smooth muscle cells of the stromal area (fibromuscular) in normal and benign hyperplastic prostatic tissue. In benign prostatic hyperplasia a significant increase in the relative amount of organelles in the smooth muscle cell was found, indicating an activation of these cells. Light microscopic analysis has revealed that benign prostatic hyperplasia is primarily a stromal disease.
Non-specific granulomatous prostatitis is an inflammatory response of a foreign body type to extravasated prostatic fluid. Its significance is incident to its frequent confusion with carcinoma of the prostate. Noteworthy is the rapidity of onset of irritative and obstructive symptoms in a relatively younger age group than one generally sees in carcinoma of the prostate. Tissue diagnosis in those suspected of carcinoma of the prostate should be established by needle biopsy and conservative measures used for at least 4 weeks in the treatment of obstructive symptoms to allow the inflammatory response to subside before intervening surgically . Most patients frequently have associated benign prostatic hyperplasia with persistent obstructive symptoms and significant residual urine. Transurethral resection of the prostate has been performed in this study without postoperative complications.
With a view to detecting early biochemical changes in diseased prostate glands, polyamines, zinc, cholesterol, and physical measurements of pH and specific gravity were determined in expressed prostatic secretion. The pH of prostatic secretion from normal men was found to be higher than previously reported in the literature. The other measured substances and specific gravity were found to be decreased in prostatitis whereas the specific gravity was markedly elevated in those patients with adenocarcinoma. Clarification of physicochemical studies on prostate secretion may lead to a system of better monitoring the course of prostate disease.
Rat ventral prostate of adult male rats contain a large amount of prostatic binding protein (PBP). Immunological evidence indicates that this protein is a specific secretion product of this gland. The amount and concentration of PBP in ventral prostate show marked changes as a function of age. PBP is low but detectable (0.009 and 0.002 U/mg prostate) in 5- and 10-day-old rats and increases thereafter in a biphasic way to adult levels (0.619 U/mg prostate). After castration of PBP drops to 0.054 U/mg prostate after 10 days and 0.030 U/mg prostate after 21 days. The concentration of PBP returns to precastration levels after 2 weeks of androgen treatment. Estradiol and progesterone are ineffective in this respect. The antiandrogen, cyproterone acetate, counteracts the stimulatory effect of testosterone propionate.
Twenty patients were skin tested with solubilized components of autologous prostatic adenocarcinoma or benign prostatic hypertrophy (BPH). Four of ten patients bearing adenocarcinoma of the prostate exhibited tumor-specific cutaneous responsiveness to solubilized autologous tumor-specific antigens (TSA). One responding patient also responded to solubilized allogeneic TSA. A single patient bearing prostatic carcinoma responded only to solubilized components of allogeneic BPH. Nine of ten patients with BPH exhibited no response to solubilized components of autologous BPH. The patient responding to the extract of autologous BPH, however, also had clinical stage B adenocarcinoma of the prostate. These observations suggest host responsiveness to TSA of prostatic carcinoma. Possible clinical significance and mechanisms to explain the findings are discussed.
Vascular supply and architecture of the prostate are studied by 100 arteriographic surveys of the pelvis. The prostatic arterial supply can be differentiated in urethral and capsular branches. In a further group of 38 patients with prostate gland disease selective bilateral arteriographies of the internal iliac arteries were performed. In 18 patients with the clinical diagnosis of prostatic adenoma, arteriography detected a carcinoma of the prostate gland. These diagnoses were proven by microscopy. In 10 patients with clinically suspected carcinoma, 5 were diagnosed by arteriography as malignant and also confirmed microscopically. The predominant angiographic criteria of prostatic carcinoma are irregular spotted stain of the involved parenchyma, hypervascularity of the urethral vascular branches, and pathological vessels.