The biological significance of atypical hyperplasia of the prostate

Summary In tissue biopsies and resection material (TUR) of the prostate a high coincidence (49.4%) was found between atypical primary hyperplasia with atypical-dysplastic microglandular, adenomatous and cribriform structures on the one hand and carcinomas on the other. The frequency of atypical hyperplasia in prostatic tissue without carcinoma was 2.8%. Microglandular pattern predominates in atypical hyperplasia combined with differentiated adenocarcinomas. A high coincidence between cribriformly structured glands of atypical primary hyperplasia and solid anaplastic — cribriform carcinomas can be observed.Autoradiographically the labeling index of atypical hyperplasia was three times as high as that of simple hyperplasia. The mean labeling index of atypical hyperplasia, however, was similar to that of poorly differentiated adenocarcinomas and cribriform carcinomas. The similar proliferation pattern of atypical hyperplasia and carcinomas as well as the high coincidence between both indicate that severe atypical primary hyperplasia is a precancerous lesion.Therefore, those patients with primary atypical hyperplasia with distinct cellular and structural atypia but without manifest carcinomas in prostatic biopsy or resection material should be followed up at short intervals.Supported by Landesamt für Forschung, Minister für Wissenschaft und Forschung des Landes Nordrhein-Westfalen, Düsseldorf     

Disorders related with ageing in the gerbil female prostate (Skene’s paraurethral glands)

The female organs, which are regulated by steroid hormones, are targets of studies especially those related to senescence. However, although the female prostate is an organ influenced by hormones and susceptible to lesions, there is still little information about its histopathology. Thus, given the morphophysiological similarity between the prostate in women and female gerbils, the present study aimed to identify the spontaneous histopathological changes in this rodent to provide contributions to the understanding of lesions that also affect the human female prostate. The structural, ultrastructural, immunohistochemical, morphometric‐stereological and serological aspects, as well as the quantification of the incidence, multiplicity and percentage of acini affected by different lesions were analyzed. Benign prostate lesions including hyperplasia, prostatitis, microcalculi and calculi; preneoplastic lesions like dysplasias; premalignant lesions, such as high grade prostatic intraepithelial neoplasia as well as malignant ones, specifically adenocarcinoma, were identified in the adult gland, but they were intensified during senescence, which is possibly due to the imbalance among steroid hormone levels. Although clinical attention focuses on other urogenital organs, the real condition of the histopathological injuries in the human female prostate should be considered. A serious preventive work regarding the female prostate could be applied in the gynaecological context in order to monitor the gland and avoid possible disturbances to women’s health and consequently provide better quality of life.     

Exposure to ethinylestradiol during prenatal development and postnatal supplementation with testosterone causes morphophysiological alterations in the prostate of male and female adult gerbils

Steroids perform significant functions in prostatic development and growth, so that interferences of this equilibrium may predispose the gland to the development of diseases during the life. Embryonic and neonatal exposure to xenoestrogens, many of them with endocrine-disrupting potential, has been related to the induction of disturbances in reproductive system organs. Thus, this study aimed to analyse morphological and immunocytochemical aspects of prostate in both male and female adult gerbils either exposed to ethinylestradiol during the prenatal phase (pregnant females received 10 μg/kg, by gavage) (EE group) or exposed to testosterone (1 mg/kg) during the postnatal period (EE/T group). Serological analysis revealed a rise in estradiol levels in adult males and females of the EE group. A higher incidence of prostatic intraepithelial neoplasia (PIN) was observed in the male and female prostate of the treated groups, besides an increase in collagen and reticular fibres. Immunocytochemistry showed an increase in prostatic epithelial cells immunoreactive to AR and a presence of a smooth muscle layer, evidenced by α actin, in injured regions this way absent in prostatic epithelial buds. These pieces of evidence suggest that the alterations verified in the prostate in adulthood of both sexes may be due to the high oestrogen levels. Either males or females of the EE/T group showed normalized estradiol levels, although prostatic lesions could be observed. While the prostatic gland of male gerbils was more affected than the female prostate, this study showed that the exposure to EE during this critical period of development disrupts the prostate of both sexes in terms of prostatic lesions.     

前列腺病变中E-cadherin、p16和ER表达及意义

目的 探讨抑癌基因E-cadherin(E-cad)、p16蛋白及ER在前列腺病变组织中的表达及临床意义。方法 应用免疫组化技术检测13例良性前列腺增生，10例高级别前列腺上皮内瘤变和20例前列腺癌组织中E-cad、p16及ER的表达。结果 前列腺癌中，E-cad表达明显减低，p16蛋白表达增加；发生转移的癌中E-cad蛋白表达显著减弱；p16蛋白的表达在HGFPIN组与低Gleason评分前列腺癌组间差异存在显著性。ER在所有前列腺病变的上皮中无表达。结论 E-cad和p16蛋白的免疫组化检测，结合血清PSA水平可作为前列腺癌诊断的辅助手段；p16蛋白的检测有助于HGPIN与高分化癌的鉴别；E-cad蛋白的表达可作为判断预后的指标。ER阴性表达并不意味雌激素治疗无效。     

Progesterone as a morphological regulatory factor of the male and female gerbil prostate

Testosterone (T) and oestrogen are the main active steroid hormones in the male and female reproductive system respectively. In female rodents progesterone (P4), together with testosterone and oestrogen, has an essential role in the regulation of the oestrous cycle, which influences the prostate physiology through their oscillations. In this work we investigated how the male and female prostate gland of Mongolian gerbils responds to surgical castration at the start of puberty and what are the effects of T, oestradiol (E2) and P4 replacement, using both quantitative and qualitative methods. We also examined the location of the main steroid receptors present in the prostate. In the castrated animals of both sexes an intense glandular regression, along with disorganization of the stromal compartment, and abundant hyperplasia was observed. The replacement of P4 secured a mild recovery of the glandular morphology, inducing the growth of secretory cells and restoring the androgen receptor (AR) cells. The administration of P4 and E2 eliminated epithelial hyperplasia and intensified gland hypertrophy, favouring the emergence of prostatic intraepithelial neoplasia (PIN). In animals treated with T and P4, even though there are some inflammatory foci and other lesions, the prostate gland revealed morphology closer to that of control animals. In summary, through the administration of P4, we could demonstrate that this hormone has anabolic characteristics, promoting hyperplasia and hypertrophy, mainly in the epithelial compartment. When combined with E2 and T, there is an accentuation of glandular hypertrophy that interrupts the development of hyperplasia and ensures the presence of a less dysplastic glandular morphology.     

Effects of radiation on the normal prostate gland

Prostate cancer is one of the commonest tumours of adult males. It shows a range of biological behaviour: many tumours are discovered incidentally; others will kill by producing widespread metastatic disease. Despite the fact that radiation is frequently used in the treatment of a range of pelvic lesions, including adenocarcinoma of the prostate itself, studies on the morphological changes in the normal prostate gland after irradiation are limited. This seems particularly surprising following the increasing use of needle biopsy specimens to assess the prostate. Patients who receive pelvic irradiation often suffer from lower urinary tract symptoms such as frequency and dysuria and it is possible that these may be related to prostatic and/or periprostatic injury. We therefore investigated the prostate glands removed at cystoprostatectomy for transitional cell carcinomas of the bladder which had received radiotherapy pre-operatively. The changes were compared to control prostatic tissue from transurethral resection specimens for benign myoadenomatous hyperplasia. We found a range of inflammatory, fibrotic and reactive cytological features, including many of the changes seen in benign hyperplasia, but these were significantly more exaggerated in the post-radiation group. In addition intraprostatic vascular and neural changes were prominent. This study documents radiation-induced changes throughout the normal prostate gland and neighbouring soft tissue and has particular importance in current pathological practice with the increasing and widespread use of needle biopsies in the diagnosis and follow-up of prostate cancer.     

Prepubertal exposure to bisphenol‐A induces ERα upregulation and hyperplasia in adult gerbil female prostate

Prostate physiology is highly dependent on oestrogenic and androgenic homeostasis. Interferences in this equilibrium, especially in early periods of life, may disrupt the prostate and increase the susceptibility to the development of diseases with ageing. Taking this into account, and considering the increase of environmental chemicals with endocrine‐disrupting potential such as bisphenol‐A (BPA), this study aimed to evaluate the prostates of adult female gerbils exposed to BPA and BPA plus testosterone from pubertal to adult periods. Morphological, stereological and chemical analyses revealed that long‐term BPA exposure, even in environmental dosages, increases the proliferative status of the prostate, increases the number of ERα‐positive stromal cells and elicits the development of prostatic hyperplasia in adult female gerbils. Moreover, we also observed that the association with testosterone did not increase the proliferative status of the gland, which shows that low levels of BPA are enough to cause an oestrogenic disruption of the prostate in young adults. This evidence suggests that this oestrogenic endocrine disruptor may increase the susceptibility to prostatic disorders with ageing.     

Immunohistochemical estrogen receptor demonstration in the prostate and prostate cancer

Immunohistochemical investigations of human prostate and human prostate cancer were performed using two different monoclonal antibodies for the demonstration of estrogen receptors (ER). One marked the nuclear estrogen receptor protein (ERICAR, Abbott Laboratories), whereas the other one marked an estrogen receptor-associated cytoplasmic protein (ER-D5 kit, Amersham Buchler). 12 transurethral resection specimens with benign prostatic hyperplasia and 10 prostatic carcinomas were investigated by ERICA. Only in 1 specimen was a focally ERICA-positive basal cell hyperplasia found. The ER-D5 kit yielded a constantly positive reaction of stromal cells, especially smooth muscle cells. Basal cell hyperplasia and squamous metaplasia, alterations which can occur during estrogen application, were always strongly ER-D5-positive. Eleven (13.4%) out of 82 prostate carcinomas were focally positive. The staining results with ER-D5 are in good accordance with biochemical estrogen receptor investigations which demonstrated the estrogen receptors especially in the fibromuscular stroma. Furthermore, the results show that therapeutically applied estrogens do not directly inhibit the growth of prostatic carcinoma, however, the effect is an indirect one by suppressing androgen synthesis of the testis. The different staining results with ER-D5 and ERICA can be explained by the low ER concentration of prostate, the concentration is evidently below the limits of detectability with ERICA.     

Malignant phyllodes tumor of the prostate: retrospective review of specimens obtained by sequential transurethral resection

A case of malignant phyllodes tumor of the prostate in a 67-year-old man is reported. The patient was referred to a hospital for urinary retention. From material taken at three transurethral resections of the prostate (TURP), a histological diagnosis of benign prostatic hyperplasia was made. However, at the fourth TURP, phyllodes tumor was diagnosed due to the presence of elongated epithelial ducts and proliferating cellular stroma with mitosis and nuclear atypia. Two months later, total cystoprostatectomy was performed. Histologically, the tumor was composed of dysplastic stromal cells and irregularly elongated epithelial ducts. Five months later the patient developed multiple lung and pelvic lymph node metastases and died. This report documents progression to a higher histological grade of prostatic phyllodes tumor documented with sequential pathological findings obtained from four TURP and surgical specimens over about 3 years.     

Frequent expression of the multi-drug resistance-associated protein BCRP/MXR/ABCP/ABCG2 in human tumours detected by the BXP-21 monoclonal antibody in paraffin-embedded material

The expression and cellular localization of angiotensin II (Ang II) and AT(1) receptor proteins were examined in the normal human prostate and benign prostatic hyperplasia (BPH) by immunohistochemistry. In the normal prostate, Ang II immunoreactivity was localized to the basal layer of the epithelium and AT(1) receptor immunostaining was found predominantly on stromal smooth muscle and also on vascular smooth muscle of prostatic blood vessels. Ang II immunoreactivity was markedly increased in hyperplastic acini in BPH compared with acini in the normal prostate (normal: 7.4+/-0.2%, n=5 vs. BPH: 22.7+/-1.9%, n=5, p<0.001). However, AT(1) receptor immunoreactivity was significantly decreased in BPH compared with the normal prostate [normal: 16.4+/-2.2%, n=4 vs. BPH: 9.4+/-1.3%, n=5, p<0.05 (p=0.025)]. The present study demonstrates the presence of Ang II peptide in the basal layer of the epithelium and AT(1) receptors on stromal smooth muscle, suggesting that Ang II may mediate paracrine functions on cellular growth and smooth muscle tone in the human prostate. Furthermore, AT(1) receptor down-regulation in BPH may be due to receptor hyperstimulation by increased local levels of Ang II in BPH. These data extend previous findings in support of the novel concept that overactivity of the renin-angiotensin system (RAS) may be involved in the pathophysiology of BPH.     

Codistribution of procathepsin B and mature cathepsin B forms in human prostate tumors detected by confocal and immunofluorescence microscopy

Cathepsin B (CB) is involved in invasion and metastasis of a variety of solid organ tumors, including human prostate cancer. The tertiary structures of the proenzyme and mature forms of CB are related closely, as revealed by crystallographic studies. However, the cellular distributions of the CB forms have not been defined in human prostate and its tumors. Our objective was to investigate the distribution and codistribution of CB and procathepsin B (proCB) in human prostate tumors. Human prostate tissue samples that were obtained from 21 prostatectomy and/or cystectomy patients were collected immediately after surgery and processed for this study. We used a rabbit antihuman liver CB immunoglobulin G (IgG) that recognizes both mature CB and proCB and a mouse antipropeptide monoclonal antibody IgG that recognizes only proCB. Fluorescein isothiocyanate (FITC)-conjugated donkey antirabbit IgG and indocarbocyanine (Cy3; rhodamine)-conjugated donkey antimouse IgG were used to differentiate localization of the enzyme forms. Immunofluorescence of FITC and Cy3 was examined in prostate sections by using epifluorescence and confocal laser-scanning microscopy. Because fluorescence is dependent on section thickness, time needed for study and photography, and the antigenic sites of proCB and mature CB localized by antibodies and by fluorescent markers (Cy3 vs. FITC), the cellular distributions and the relative intensity of fluorescence on cryostat sections were assessed qualitatively. Immunofluorescence of Cy3 for localizing proCB and of FITC for localizing mature CB were observed in prostatic epithelial cells and their tumors and in stromal connective tissue cells. By using confocal microscopy, colocalization of the enzyme forms in the same cells was indicated by yellow fluorescence. In stromal cells (such as smooth muscles, fibroblast, and macrophages), the distribution of proCB and relative fluorescence intensity was moderate to predominant in human prostate and its tumors. In neoplastic prostate, the cellular distributions of CB ranged from low to predominant levels. In some neoplastic glands, Cy3 fluorescence for proCB was absent, whereas the mature form of CB localized in cancer cells and in the subjacent extracellular matrix. Confocal microscopy showed a close association of CB with extracellular matrix surrounding neoplastic acini and invasive cells, indicating that the enzyme form was probably involved in degradation of the matrix proteins. The negative control study showed no specific immunofluorescence for proCB or CB in prostate cancer cases. We have shown a differential distribution of proenzyme and mature forms of CB in normal prostate, benign prostatic hyperplasia, and neoplastic prostate. The enzyme forms were assessed by determining the cellular distributions of CB and proCB. Our study indicates that the differential distribution of proCB and CB might provide clues into aggressiveness of prostate cancers within Gleason grades. However, we emphasize that our observation should be evaluated in a larger series of prostate samples before a definitive conclusion can be reached. This is the first report to show codistribution of proenzyme and mature forms of CB by using confocal microscopy. Anat. Rec. 252:281–289, 1998. © 1998 Wiley-Liss, Inc.     

Neonatal exposure to ethinylestradiol increases ventral prostate growth and promotes epithelial hyperplasia and inflammation in adult male gerbils

The aim of this study was to analyse morphologically the ventral prostate of adult Mongolian gerbils exposed to ethinylestradiol (EE) during the first week of postnatal development. Lactating females received daily, by gavage, doses of 10 μg/kg of EE diluted in 100 μl of mineral oil from the 1st to 10th postnatal day of the pups (EE group). In the control group (C), the lactating females received only the vehicle. Upon completing 120 days of age, the male offspring were euthanized and the prostates collected for analyses. We employed morphological, stereological‐morphometrical, immunohistochemical and ultrastructural methods. The results showed that the postnatal exposure to EE doubled the prostatic complex weight, increasing the epithelial and stromal compartments, in addition to the secretory activity of the ventral lobe of the prostate. All glands exposed to EE showed strong stromal remodelling, and some foci of epithelial hyperplasia and inflammatory infiltrate in both luminal and epithelial or stromal compartments. Cells positive for anti‐AR and anti‐PCNA reactions increased into the epithelial and stromal tissues. ERα‐positive cells, which are normally found in the stromal compartment of intact prostates, were frequently observed in the prostatic epithelium of treated animals. This study demonstrated that the exposure to EE during postnatal development causes histophysiological alterations in this gland, predisposing to the development of prostatic lesions during life. These results are important for public health, considering that women worldwide have commonly used EE. Moreover, the bioaccumulation of this chemical has increased in different ecosystems.     

Prostate carcinogenesis induced by N-methyl-N-nitrosourea (mnu) in gerbils: Histopathological diagnosis and potential invasiveness mediated by extracellular matrix components

In the present study prostate lesions were induced in gerbils (Meriones unguiculatus) treated with a single N-methyl-N-nitrosourea (MNU) dose; thus, the incidence, latency and histology of these lesions were evaluated. Fibrillar elements of the extracellular matrix associated with microinvasive sites were also investigated. Animals were divided into 5 groups, including 2 control groups: (1) remained untreated; (2) received the corn oil vehicle (vehicle, 0.1 ml/application) and three different tumor induction regimens: (1) received MNU (30 mg/kg) and weekly testosterone (2 mg/kg) (MNU + testosterone); (2) received only MNU (30 mg/kg); (3) received weekly testosterone doses (2 mg/kg). After 3 and 6 months the animals were dissected and the prostates were evaluated morphologically, immunohistochemically and quantitatively. MNU plus androgen contributed to the development of prostatic intraepithelial neoplasia, microinvasive carcinoma and adenocarcinoma in gerbil prostate. However, these lesions occurred earlier in time in groups that received MNU and androgen compared to control animals as they over time also developed to a high extent microinvasive lesions. Cytochemistry and immunohistochemistry showed that these injuries were commonly associated with inflammatory cells whereas the epithelial cells presented proliferative activity. The α-methylacyl-CoA racemase (AMACR) expression in prostate cancer cells facilitated diagnosis of gerbil lesions. Testosterone, MNU and MNU + testosterone showed an increased epithelial volume, although the secretory activity was significantly suppressed mainly at neoplastic foci. In the prostatic stroma, reticular fibers increased significantly in MNU, MNU + testosterone and among the lesions found in these groups, while collagen fibers decreased at neoplastic sites. The disruption of the basement membrane was proven at malignant sites by ultrastructural analysis and type IV collagen and laminin degradation. The prostate carcinogenesis mediated by MNU and androgen stimulated the emergence of proliferative lesions in gerbils after short periods and showed the importance of a dynamic remodeling of stromal components for cellular invasiveness.     

Chronic caffeine intake increases androgenic stimuli,epithelial cell proliferation and hyperplasia in rat ventral prostate

Coffee intake has been associated with a low risk of developing cancer, including prostate cancer, which is one of the most commonly diagnosed cancer in men. However, few studies have evaluated the chronic effects of caffeine, which is the most abundant methylxanthine in coffee, on prostate morphology and physiology. In the present study, we investigated the effects of chronic, low‐dose caffeine intake on rat prostate morphology from puberty to adulthood. Five‐week‐old male Wistar rats were randomized into two experimental groups: caffeine‐treated (20 ppm in drinking water, n = 12) and control (n = 12). The ventral and dorsolateral prostates were dissected, weighted and submitted to morphological, morphometrical and immunohistochemical analysis of cellular proliferation, apoptosis and androgen receptor (AR) tissue expression. The testosterone (T) and dihydrotestosterone (DHT) concentrations were measured in the plasma. Our results show that caffeine intake increased the concentrations of T and DHT, organ weight, epithelial cell proliferation and AR tissue expression in the ventral prostatic lobe. All the ventral prostates from the caffeine‐treated animals presented various degrees of epithelial and stromal hyperplasia. Our results suggest that chronic caffeine intake from puberty increases androgenic signalling and cell proliferation in the rat prostate gland and can be related to the development of benign prostatic hyperplasia.     

Sclerosing adenosis of the prostate. Report of three cases with electronmicroscopy and immunohistochemical study

Three cases of rare variant of prostatic adenosis with the features of sclerosing adenosis, an uncommon lesion sometimes confused with prostatic carcinoma, are reported. The lesions consisted of a small, single nodule in prostates otherwise showing typical adenomatous and fibromuscular hyperplasia. The lesions were composed of crowded small glands, small solid nests and individual cells embedded in a cellular stroma. Immunohistochemistry showed that the glands were lined by basal cells positive for the high-weight keratins (EAB-903 and AE-3), a finding which confirms the benign nature of the lesion. S-100 protein and smooth muscle actin were also positive in the same basal cells suggesting myoepithelial differentiation, a character not found in basal cells outside this lesion. This finding was confirmed at ultrastructural level by the finding of numerous thin filaments in the cytoplasm of basal cells. It is important to recognize this lesion in order to avoid confusion with well-differentiated prostatic carcinoma.     

A human prostatic bacterial isolate alters the prostatic microenvironment and accelerates prostate cancer progression

Inflammation is associated with several diseases of the prostate including benign enlargement and cancer, but a causal relationship has not been established. Our objective was to characterize the prostate inflammatory microenvironment after infection with a human prostate‐derived bacterial strain and to determine the effect of inflammation on prostate cancer progression. To this end, we mimicked typical human prostate infection with retrograde urethral instillation of CP1, a human prostatic isolate of Escherichia coli. CP1 bacteria were tropic for the accessory sex glands and induced acute inflammation in the prostate and seminal vesicles, with chronic inflammation lasting at least 1 year. Compared to controls, infection induced both acute and chronic inflammation with epithelial hyperplasia, stromal hyperplasia, and inflammatory cell infiltrates. In areas of inflammation, epithelial proliferation and hyperplasia often persist, despite decreased expression of androgen receptor (AR). Inflammatory cells in the prostates of CP1‐infected mice were characterized at 8 weeks post‐infection by flow cytometry, which showed an increase in macrophages and lymphocytes, particularly Th17 cells. Inflammation was additionally assessed in the context of carcinogenesis. Multiplex cytokine profiles of inflamed prostates showed that distinct inflammatory cytokines were expressed during prostate inflammation and cancer, with a subset of cytokines synergistically increased during concurrent inflammation and cancer. Furthermore, CP1 infection in the Hi‐Myc mouse model of prostate cancer accelerated the development of invasive prostate adenocarcinoma, with 70% more mice developing cancer by 4.5 months of age. This study provides direct evidence that prostate inflammation accelerates prostate cancer progression and gives insight into the microenvironment changes induced by inflammation that may accelerate tumour initiation or progression. Copyright © 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

Florid basal cell hyperplasia of the prostate

Florid basal cell hyperplasia of the prostate is an uncommon proliferative condition, most often associated with adenomatous hyperplasia. It is considered a benign lesion although confusion with prostatic cancer is possible when one is not familiar with the histopathological appearance. We report another two cases of the glandular type of basal cell hyperplasia with immunohistochemical findings. Both lesions were composed of crowded and rather small glands with piling up of basaloid cells. They showed immunohistochemical positivity for high molecular weight cytokeratin 34βE12, confirming their relationship with basal cells. We detected focal positivity of these basal cells for α-smooth muscle actin, suggesting myoepithelial differentiation. Paucity of actin-positive smooth muscle cells in the stroma was noticed. One of the lesions showed some mild cytological atypia with prominent nucleoli and increased mitotic activity.     

Long-term inhibition of 5-alpha reductase and aromatase changes the cellular and extracellular compartments in gerbil ventral prostate at different postnatal ages

As local steroid metabolism controls the bioavailability of active steroidal hormones in the prostate, the aim of this study, was to investigate the effects of absence of 5-alpha reductase (5α-r) and aromatase ( Aro ) enzymes on prostatic cellular and extracellular components after long-term inhibition. Young, adult and old male Mongolian gerbils were treated orally, once a day, for 30 consecutive days, with Finasteride (10.0 mg/kg) and Letrozole (1.0 mg/kg) (5α-r and Aro enzymes inhibitors respectively) simultaneously or separately. Animals were killed on 1, 7, 14 and 21 days post-treatment. Data obtained after double or single enzymatic inhibition with Finasteride and Letrozole demonstrated marked remodelling of epithelial and stromal compartments. During the post-treatment period, particularly on the first and the last analysed days, prostatic epithelial cells showed decreased cytoplasmic volume and secretory activity. In the stroma, collagen fibres had accumulated in the epithelial base and among smooth muscle cells, which showed reduced diameter and condensed cytoplasm, and some of them had a highly irregular external contour. Also in the sub-epithelial area, some fibroblasts acquired an activated phenotype besides increased deposits of amorphous granular material. In conclusion, the inhibition of 5α-r and Aro enzymes affected, in a persistent manner, the structural and ultrastructural morphology of the prostate, irrespective of the gerbil's age. Hence these enzymes appear to be crucial in the maintenance of this gland during postnatal development. Also, these data bring more light to the complex issue of the mechanisms of local steroid metabolism and prostatic histology. Thus, the blockade of the steroid-metabolizing enzymes provided an important novel tool to study the relationship between sex steroids and normal physiology and diseases of the prostate.     

Hybrid sclerosing adenosis and basal cell hyperplasia of the prostate

Hybrid sclerosing adenosis and basal cell hyperplasia of the prostate is a rare lesion. Here we report the seventh case of such lesions. Histological examination of the transurethral resection of the prostate of a 83-year-old Japanese man showed a small lesion consisted of sclerosing adenosis and basal cell hyperplasia, in addition to the diffuse glandular and fibromuscular hyperplasia. Immunohistochemically, many basal cells in sclerosing adenosis and basal cell hyperplasia areas showed a positive reaction for p63, cytokeratin 5, and D2-40. Additionally, many basal cells in the sclerosing adenosis area and some basal cells in the basal cell hyperplasia area were positive for S-100 protein and alpha-smooth muscle actin, which are myoepithelial cell markers. Finally, we suggest that hybrid sclerosing adenosis and basal cell hyperplasia may be actually a special form of hyperplastic lesion of all components of prostatic tissue, reflecting the unbalanced distribution of glandular, stromal (sclerosing adenosis), and basal cell hyperplasia with the differentiation toward myoepithelial cells predominantly occurring in a sclerosing adenosis area. Additionally, this case showed that D2-40 is a useful marker of basal cells.     

Expression of KAI1 in paraffin-embedded normal, hyperplastic and neoplastic prostate and prostate carcinoma cell lines

Expression of KAI1, a tumor metastasis suppressor gene, was studied with different fixatives in frozen and paraffin-embedded sections of human and rat prostate carcinoma cell lines and human prostate lesions by Immunohisto-chemistry. Immunoreactivity of the membrane antigen in cell lines was associated with known expression levels in these lines and the fixative used. Formalin and paraformaldehyde helped maintain the immunoreactivity of cells. In human prostate, frozen sections revealed diffuse reactivity of the antigen in normal and neoplastic tissues while paraffin-embedded tissues usually showed focal reactivity, although more than 50% of cases with normal epithelium and adenocarcinomas were reactive. In some cases, pretreatment with trypsln enhanced immunoreactivity. Benign prostatic hyperplasia (BPH) showed the most intense diffuse immunoreactivity, which suggested enhanced expression. Prostatic intraepithelial neoplasia (PIN) also often expressed high levels of KAI1. Three of five metastases were reactive but two primaries and their metastases were not. Lymphocytes in primary carcinomas and lymphocytes and germinal center cells in lymph nodes were immunoreactive, while adjacent primary or metastatic prostate adenocarcinoma epithelium was not immunoreactive. Although paraffin-embedded human tissues were not optimal for determining levels of expression of KAI1, they did show immunoreactivity that could have prognostic value and showed the specific cytoplasmlc localization of the protein in cells.