Stromal and acinar components of the transition zone in normal and hyperplastic human prostate

OBJECTIVE: To analyse the histological components of the transition zone in both normal human prostate and benign prostatic hyperplasia (BPH), and to determine the volumetric density (Vv) of the different elements (connective tissue, smooth muscle cells, acini and total stroma). MATERIALS AND METHODS: Samples of BPH tissue from the transition zone were obtained from 16 patients with clinical symptoms of bladder outlet obstruction who underwent open prostatectomy. The control samples comprised 16 transition zone samples from prostates obtained during necropsy of adults aged < 30 years (killed in accidents). The Vv of these components was determined by stereological methods. RESULTS: The mean (sd) Vv in the controls and BPH samples were, respectively: connective tissue 40.47 (5.16) and 46.71 (9.91)%; smooth muscle cells 24.86 (2.74) and 31.56 (5.49)%; acini 28.73 (6.25) and 17.78 (10.87)%; all differences were statistically significant. CONCLUSIONS: These results confirm the hypothesis that in BPH there is an increase in the stromal component, both smooth muscle fibres and connective tissue.     

Densitometric and morphometric evaluation of growth in primary cultures of rat ventral prostate epithelial cells

This study describes a method for establishing primary cultures in 24-well culture vessels and evaluating the effects of serum, hormones, and other factors on cell growth using densitometry. Primary cultures of rat ventral prostate epithelial cells were grown in 24-well culture vessels containing F12K culture medium supplemented with various concentrations of the following substances: fetal bovine serum (FBS), horse serum (HS), testosterone (T), dihydrotestosterone (DHT), hydrocortisone (HC), zinc (Zn), transferrin (TR), cysteine (CYS), glutamine (GLT), selenium (SEL), and ascorbic acid (AC). The effect of each supplement on cell growth was evaluated on fixed and stained cultures using a photovoltaic cell densitometer designed to read the total culture surface of a 16-mm well. Increasing concentrations of both HS and FBS resulted in an increase in cell growth. T, Zn, HC, TR, and AC each had a stimulatory effect on cell growth. CYS, GLT, and DHT had little effect on cell growth, while SEL was inhibitory to cell growth. This data compares favorably with that obtained by other methods, such as morphometric analysis and ornithine decarboxylase production. These results indicate that densitometry is a useful method for determining the effect of supplements on cell growth in primary culture.     

Lymphocytic vasculitis of the prostate transition zone

Study Type – Pathology (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Lymphocytic vasculitis of the prostate is an exceedingly rare form of localised vasculitis that presents without systemic involvement, and is illustrated with anecdotal case reports; often as localised polyarteritis nodosa‐like vasculitis. True incidence and clinical significance of lymphocytic vasculitis of the prostate in surgical specimens is virtually unknown. The present findings support that lymphocytic vasculitis of the prostate was present in 67 (12.4%) of 540 specimens. Lymphocytic vasculitis of the prostate was present in 14 (93.3%) of 15 specimens with prostatic infarction (P < 0.001) with a risk of 124.68 (OR [odds ratio]; 95% CI [confidence interval] 16.07–967.07) as compared with BPH cases not associated with lymphocytic vasculitis.

OBJECTIVE

• ? To present our experience of lymphocytic vasculitis of the prostate in men with benign prostatic hyperplasia (BPH) without systemic involvement, as this is an exceedingly rare form of localised vasculitis and the incidence in surgical specimens and clinical significance of lymphocytic vasculitis is virtually unknown.

PATIENTS AND METHODS

• ? A sequential cohort series of 540 surgical specimens removed because of BPH‐related symptoms, including simple prostatectomy (374 men) and transurethral resection of the prostate (166), comprised the study group.
• ? All men had histological diagnosis of BPH and received surgical therapy only. None of the men had had previous surgery or granulomatous prostatitis.
• ? The mean (range) age at diagnosis was 67.8 (38–89) years.

RESULTS

• ? Lymphocytic vasculitis of the prostate was present in 67 (12.4 %) of 540 specimens. It was seen in a variable number of small‐ to medium‐sized parenchyma arteries with segmental to transmural lymphocytic inflammation, within the morphological spectrum of a polyarteritis nodosa (PAN)‐like lesion seen at the periphery of BPH nodules.
• ? In four cases, focal fibrinoid necrosis was seen in vessels with otherwise typical lymphocytic vasculitis features. Immunohistochemical staining showed a T cell predominant polymorphic cellular infiltrate with a minor component of B cells and monocytes. Six cases additionally had eosinophils (<1% of inflammatory cells).
• ? Lymphocytic vasculitis of the prostate was present in 14 (93.3%) of 15 specimens with prostatic infarction (P < 0.001) with a risk of 124.68 (odds ratio [OR]; 95% confidence interval [CI] 16.07–967.07) as compared with BPH cases not associated with lymphocytic vasculitis. Logistic regression multivariate analysis selected both lymphocytic vasculitis of the prostate and patient age as significant predictors of prostate infarction with lymphocytic vasculitis being the most significant (P < 0.001; OR 128.12; 95% CI 16.298–1007.202). Follow‐up information was available in all cases, range 2–16 years, and none of the patients developed systemic disease.
• ? A validation set of 1665 additional cases including radical prostatectomy, cystoprostatectomy, and needle biopsies showed lymphocytic vasculitis of the prostate being associated to prostate infarction on univariate and multivariate logistic regression (P < 0.001; OR 228.34; 95% CI 45.17–1154.22) analyses.

CONCLUSIONS

• ? Lymphocytic vasculitis in men with BPH is associated with prostatic infarction and should be considered a form of localised vasculitis with PAN‐like morphology that does not necessitate additional evaluation for systemic disease.
• ? The potential clinical relevance of lymphocytic vasculitis warrants further investigation.

     

Increased and localized accumulation of chondroitin sulphate proteoglycans in the hyperplastic human prostate

OBJECTIVE: To analyse by immunohistochemistry the expression of chondroitin sulphate (CS) (detected in the hyperplastic prostate and possibly affecting the proliferation of prostate cells) in benign prostatic hyperplasia (BPH) to determine its distribution and location. MATERIALS AND METHODS: Samples of BPH were obtained from 11 patients (aged 58-83 years) and controls consisting of the transitional zone of five prostates from young men aged 19-27 years. Tissue sections were labelled with antibodies against CS, perlecan, type IV collagen, laminin, and smooth muscle cell (SMC) alpha-actin. The amount of CS immunostaining was estimated by semi-quantitative scoring and correlated with prostate-specific antigen (PSA) level and prostate size. RESULTS: The anti-CS antibody faintly stained the stroma of normal prostates, but in BPH samples the staining was intense and concentrated around acini, including the periphery of adjacent SMCs. This staining pattern was totally absent in the normal samples. Type IV collagen, perlecan and laminin were homogeneously distributed in the whole stroma of both normal and BPH samples. There was no significant correlation between intensity of CS staining and either PSA or prostate size. CONCLUSIONS: The expression of CS proteoglycans is increased in BPH, where they co-locate with basement membranes of the acinar epithelium and of peri-acinar SMCs. This enhanced expression is specific for these proteoglycans, as other basement membrane components are unaffected, and this may result from the regulatory effects of local factors that are active in BPH.     

Sex steroid receptors in normal and hyperplastic human prostate

The concentrations of sex steroid receptors (per unit DNA) were measured in normal periurethral and peripheral prostatic tissue samples from seven men (mean age 64 years; range 54-71 years) undergoing cystectomy for bladder cancer, and in hyperplastic nodules from 15 men with BPH (mean age 69 years; range 60-89). Occupied androgen (AR) and estrogen (ER) receptors were measured with an improved exchange procedure, where receptor-binding sites were stabilized by a combinatorial procedure involving careful washout of extracellular secretory products (including proteases) prior to homogenization, inclusion of 0.5 mM phenylmethyl sulfonylfluoride (PMSF) and 20 mM molybdate in the exchange medium, and long-term incubation at 0-4 degrees C. Bound radioligands were separated by a hydroxylapatite (HAP) batch adsorption procedure. Maximal specific exchange binding of 3H-R 1881 or 3H-estradiol in total homogenates of human prostate samples was achieved after incubation periods of about 72 h at 0-4 degrees C. In contrast, progestin receptors (PR) were readily available for binding 3H-R 5020; thus overnight binding at 0-4 degrees C was routinely used to measure PR. Binding specificities and equilibrium binding constants (calculated from 8-point Scatchard plots, correcting for nonsaturable binding) were found to be characteristic for AR, PR, and ER, respectively. The receptor results obtained in this study demonstrate that no significant differences existed in total AR per unit DNA between hyperplastic and either central or peripheral prostatic tissue samples; PR was present in both zones of normal prostatic tissue as often as in BPH samples, with PR concentrations significantly lower in hyperplastic samples; and ER was irregularly detected in both normal and hyperplastic tissue in low concentration relative to AR and PR; the frequency of ER detection was much lower in BPH than in normal prostate tissue. Studies of steroid receptor content relative to enzyme markers specific for epithelial and stromal cells in BPH samples showed a positive correlation between acid phosphatase activity (a specific marker for epithelial cells) and both AR and PR. No correlation was observed between AR or PR with either prolyl hydroxylase or myosin ATPase (specific markers for stromal cells). These observations suggest that PR, as well as AR, is primarily associated with the epithelial elements of prostate. Because of the relative infrequency of ER, similar correlation of ER with enzyme markers was not possible.     

Immunohistochemical determination of age related proliferation rates in normal and benign hyperplastic human prostates

Summary To study whether benign prostatic growth in aging men correlates with an increase in proliferation, proliferation rates were determined immunohistochemically using the antibody Ki-67 in 20 benign hyperplastic prostates (BPH) and in four normal prostates (NPR). There was no significant correlation between age and proliferation rate in epithelium or stroma in BPH. In addition, no significant correlation between prostate weight and proliferation rate could be demonstrated in either compartment. In NPR the proliferation rate in epithelium and stroma was 9 times and 37 times lower, respectively, than in BPH. Obviously the induction of BPH from NPR may be associated with a distinct increase in proliferation. The further increase in BPH volume, however, is not correlated with a further increase in proliferation rate.     

Effect of increasing ratio of estrogen: androgen on proliferation of normal human prostate stromal and epithelial cells, and the malignant cell line LNCaP

BACKGROUND: Changes in steroid ratios seen in the aging male are thought to promote prostate disease. The aims of this study were to compare the effects of varied ratios of steroids on growth of normal stromal and epithelial cell isolates, and the prostate cancer cell line, LNCaP. METHODS: The effect of altered steroid ratios on cell proliferation of normal stromal (PrSC) and epithelial (PrEC) prostate cells, and the malignant cell line, LNCaP, were assessed. RESULTS: Increasing the ratios of both estrogen:dihydrotestosterone (DHT) and DHT:estrogen, stimulated PrSC proliferation, with increasing estrogen:DHT having the greatest effect. LNCaP proliferation was increased significantly by both steroids, but altered ratios had no additional effect. PrEC proliferation was unaffected when cells were grown alone, despite presence of androgen receptors (AR) and estrogen receptors (ER). When grown in co-culture PrEC cell proliferation was significantly increased by treatments. CONCLUSIONS: PrSC proliferation is stimulated by an increasing ratio of estrogen:androgen. Proliferation of normal epithelial cells is stimulated as a result of an indirect action of steroids mediated by stromal cells. Malignant prostate cancer cells have an altered response in comparison.     

The glycosaminoglycans of normal and hyperplastic prostate

A study has been made of the glycosaminoglycans (GAG) of the fetus, normal adult, and benign hyperplastic prostate. In the adult normal prostate dermatan sulphate (DS) is the predominant GAG. The central zone has a slightly higher chondroitin sulphate (Ch AC) content than the peripheral zone. Fetal prostates (22-27 weeks gestation) contain no heparan sulphate (HS). Benign prostatic hyperplasia (BPH) has an increased content of Ch AC. On separation of BPH stroma and epithelium, the epithelial fraction contains only Ch AC and DS. HS and hyaluronic acid (HA) are confined to the prostatic stroma.     

Human papillomavirus DNA in malignant and hyperplastic prostate tissue of black and white males

This study hypothesized that human papillomavirus (HPV) infection is associated with increased prostate cancer risk, and that the 40% higher incidence rate in blacks is attributable to a greater prevalence of oncogenic viral DNA in prostatic tissues. Viral L1 and E6 gene sequences were polymerase chain reaction (PCR) amplified in archival tissues from 56 prostate cancer cases and 42 hyperplastic controls. L1 amplimers were hybridized by dot blot to HPV L1 generic probes, as were E6 amplimers to E6 probes specific for HPV 6, 11, 16, 18, 31, 33, and 45. 12.5% of cases and 9.5% of controls were HPV positive by L1 hybridization (age/race adjusted odds ratio = 1.66, 95% confidence interval = 0.33, 8.37). Four of 52 (7.7%) blacks were HPV positive compared to 7 of 46 (15.2%) whites. However, none of the L1-positive samples hybridized to the E6 type-specific probes, and positive results were not replicable using a broader spectrum of PCR primers and probes. These data suggest that HPV infection is not a significant risk factor for prostate cancer and does not explain the excess cancer risk in blacks. © 1996 Wiley-Liss, Inc.     

Morphometric evaluation of the human prostate

In order to clarify the ageing-related histological changes in the human prostate, a quantitative morphometric analysis was performed. Complete prostates were obtained at autopsy from 281 men (aged 20-84 years) who died in traffic accidents and presented no clinical symptoms of prostatic disease. The prostates were classified as: histologically normal (n=182), with nodular hyperplasia (n=42), with intraepithelial neoplasia (n=40) and carcinomatous with low Gleason grade (n=20). Each prostate was divided into three regions (periurethral, central and peripheral) and the volume of each region, as well as the average volume occupied by stroma and epithelium in each region were quantified. For each parameter, the average values for each age group were compared. In the histologically normal prostates, an increase with ageing in the total volume and the volume occupied by the central region were observed; these increases were mainly caused by an increase in the stromal volume of the central region in men after 30 years of age. No histologically normal prostates were found in men older than 70 years of age. Nodular prostatic hyperplasia was found in men over 30 years of age and a fluctuation in the total volume throughout ageing was observed. Prostates with intraepithelial neoplasia (PIN) and carcinoma were observed in men aged >20 years and the total volume and those of each prostatic region showed multiple variations, except for the eighth decade where a marked increase with regard to that of the previous decades was observed.     

Nuclear androgen receptor content in biopsy specimens from histologically normal, hyperplastic, and cancerous human prostatic tissue

Androgen receptors (ARn) were assayed in nuclear extracts of prostatic biopsies from 60 patients with benign prostatic hyperplasia (BPH) and 82 patients with prostatic cancer (PC), with an exchange assay using heparin extraction, labelling with 3H-R1881, and protamine sulphate precipitation. The content of ARn of BPH biopsies (38 +/- 34 fmol/mg protein [mean +/- SD]; n = 70) was not different from that of PC biopsies (39 +/- 32 fmol/mg protein; n = 115). Biopsies showing essentially normal prostatic tissue had a lower ARn content (12 +/- 13 fmol/mg protein; n = 6). The content of ARn was independent of the age of the patient and of the histological grade of the carcinomas. A considerable variation in ARn content within tumors of individual patients was found, indicating that ARn are not uniformly distributed over prostatic tissue; ie, cells with high and low receptor content may coexist in different proportions in different regions of the prostate. Therefore, assays on multiple biopsies may be required for a proper estimation of the mean receptor content. The question remains, however, whether the behavior of the tumor is adequately predicted by the mean receptor level or, for instance, by the region with the lowest receptor content.     

Epithelial and fibroblastoid cell lines derived from the normal canine prostate. I. Separation and characterization of epithelial and stromal components

Cell cultures displaying exclusively epithelial or fibroblastoid morphology have been isolated by spillage and collagenase digest techniques, respectively. Primary cultures of both cell types have been readily subcultured. The use of a type I collagen substrate has been shown to be essential to the growth of normal prostatic epithelium in monolayer cultures. The ability to generate replicate subcultures of both cell types has allowed the quantitative characterization of the mitogenicity of fetal bovine serum and insulin in early subcultures. The control of culture conditions has permitted uniform cell population growth in early subculture with regular population doubling times in log phase of growth. Epithelial cultures have been shown to display many ultrastructural characteristics common to the normal epithelium of the canine prostate.     

Comparison of the zones of the human prostate with the seminal vesicle: morphology, immunohistochemistry, and cell kinetics

BACKGROUND: The prostate contains three glandular zones (central, peripheral, transition) with widely differing susceptibilities to cancer and benign prostatic hyperplasia (BPH). Most of the prostate is derived from urogenital sinus, but the central zone may be derived from Wolffian duct, in common with the seminal vesicles (SV). The peripheral zone is the most frequent site of cancer and the transition zone is the almost exclusive site of BPH. METHOD: We compared the histology and immunohistochemistry of the SV with those of the prostate zones in order to identify differences associated with susceptibility to disease or different embryological origins. Sections from the prostates of nine organ donors (aged 15-36) were stained for tissue-specific markers, antigens previously shown to stain differentially between the zones and markers of cell proliferation and cell death. RESULTS: Neuroendocrine cells were absent from the SV and significantly fewer neuroendocrine cells were seen in the central zone compared to the peripheral zone. Most of the SV epithelium stained for lactoferrin, compared to approximately one-third of central zone and only 2% of peripheral zone epithelial cells. The proliferative index of the central zone was approximately 50% lower and the incidence of apoptotic cells approximately half that of the peripheral and transition zones. CONCLUSIONS: The central zone has features in common with both the SV and the other zones of the prostate. The higher incidence of proliferative diseases in the transition and peripheral zones may be associated with the higher rate of cell turnover observed in these zones.