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Studies have shown that Gleason grade 4 extent as well as architectural subtypes provide prognostic information. We aimed to evaluate the influence on biochemical recurrence following radical prostatectomy of patients with organ-confined tumor, Gleason score 7, and negative surgical margins. Total tumor extent, Gleason grade 4 total extent and the extent of each architectural subtype (fused glands, poorly defined glands, cribriform glands, and glomeruloid glands) were evaluated by a semiquantitative point-count method using different colors to identify each subtype. Microscopic morphology of glomeruloid glands was considered regardless of morphology: size (small or large), attachment (narrow or extensive), and cribriform or solid intraluminal protrusion. Gleason grade 4 total extent significantly predicted shorter time to biochemical recurrence in univariate and multivariate analysis. Stratifying extent, Gleason grade 4 with >30% of the total grade 4 extent was significantly predictive for time of recurrence. Considering architectural subtypes, cribriform and glomeruloid glands but not fused and poorly formed glands extent, significantly predicted shorter time to recurrence in univariate analysis. An important issue related to the studies on prognostic significance of Gleason grade 4 subtypes is the lack of uniformity in the definition of microscopic morphology of the subtypes particularly of the glomeruloid architecture.

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Purpose:To quantify and compare the expression of stromal elements in prostate adenocarcinoma of different Gleason scores with non-tumor area (control).Methods:We obtained 132 specimens from samples of prostate peripheral and transition zone. We analyzed the following elements of the extracellular matrix: collagen fibers, elastic system, smooth muscle fibers and blood vessels. The tumor area and non-tumor area (control) of the TMA (tissue microarray) were photographed and analyzed using the ImageJ software.Results:The comparison between the tumor area and the non-tumor area showed significant differences between stromal prostate elements. There was an increase of collagen fibers in the tumor area, mainly in Gleason 7. Elastic system fibers showed similar result, also from the Gleason 7. Blood vessels showed a significant increase occurred in all analyzed groups. The muscle fibers exhibited a different behavior, with a decrease in relation to the tumor area.Conclusions:There is a significant difference between the extracellular matrix in prostate cancer compared to the non-tumor area (control) especially in Gleason 7. Important modifications of the prostatic stromal elements strongly correlate with different Gleason scores and can contribute to predict the pathological staging of prostate cancer.(AU)

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Senescence is one of the main aetiological factors which are responsible for natural androgen ablation in men and occurrence of prostatic diseases. However, it is unclear how the prostatic lesions are signallised in the prostate. Thus, the aim of this study is to characterise the structural, the ultrastructural and the proliferative aspects of the peripheral prostatic zone in the elderly men with and without diagnoses of prostatic lesions and with potential precursors of prostate cancer. Sixty samples of prostatic tissue, from 60 to 90-year-old patients with and without lesions obtained from autopsied or prostatectomised patients were divided into four groups (15 samples per group): standard group (no lesions), benign prostatic hyper-plasia group, high-grade prostatic intra-epithelial neoplasia group and prostatic carcinoma group. The samples were submitted to morphometrical, structural and ultrastructural analyses in addition to cellular apoptosis and proliferative analyses. The results showed morphological damages in the stroma and cellular organelles involved in the secretory process of the prostate. Moreover, the prostatic lesions in elderly men demonstrated disturbance in the proliferation/apoptosis rate, indicating a prevalence of the proliferative process. Finally, the imbalance in prostatic stroma-epithelium interaction was a harmful feature in the elderly men as a result of structural changes, which are crucial factors for the development and progression of carcinogenesis.

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Differently graded areas of human prostate adenocarcinoma were examined after Masson's trichrome staining or immunohistochemistry for smooth muscle alpha-actin, type IV collagen and laminin. In addition, the ultrastructure of the prostatic smooth muscle cells (SMC) during glandular proliferation and epithelial invasion in selected tumors was studied. The SMC formed a thick layer below the epithelial structures in unaffected areas and were closely associated with each other in homotypic interactions. As the tumor grade increased, the SMC gradually lost interactions with each other and became atrophic. With the growth of the epithelial compartment, the SMC initially segregated to the tumor periphery and the intercellular spaces increased. In high grade tumors, the epithelial cancer cells invaded the spaces between the SMC. Immunohistochemical analysis of the basal membrane revealed increased disruption of the usually thick basal membrane, which became thinner and faintly stained with each of the antibodies used. We conclude that most SMC become atrophic following epithelial invasion in human tumors and that degradation of the basal membrane is an important factor in this process. At the ultrastructural level, different SMC phenotypes occur in prostatic tissues during epithelial invasion. Interconversion between these phenotypes is suggested and a probable relationship among them is proposed.

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The Meriones unguiculatus (Mongolian) gerbil has demonstrated significant prostatic responses to hormonal treatments, and to drugs against human prostatic hyperplasia. Spontaneous neoplasia develops in the older animals. Thirty gerbils (age 18 months) were divided into non-affected and prostatic lesion bearers and the prostate lesions were evaluated morphologically, immunohistochemically and quantitatively. The most frequent changes were in epithelial sites and, namely prostatic intraepithelial neoplasias, microinvasive carcinomas and adenocarcinomas. In the stromal compartment, cellular hyperplasia, when verified, was always associated with the sites of anomalous epithelium. Additionally, larger deposition of collagen fibrils, generating stromal fibrosis, was found in all the old gerbils analysed. The quantitative analysis showed that prostatic tissue proportions differed in altered areas, being specific for each lesion type. Isolated nuclear and nucleolar parameters were not effective in diagnosing the malign potential of lesions. However, the cellular proliferation and death indexes indicated larger cellular turnover in invasive lesions such as carcinomas. With these analyses, it could be verified that old gerbils present high propensity to develop spontaneous prostate changes and this may aid in a better understanding of the biological behaviour of human prostate cancer.

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Six microsomal population of estradiol and androgen receptors have been characterized in human benign prostatic hypertrophy (BPH) and prostate cancer (PCa). Estradiol receptor (ER) and androgen receptors (AR) were extracted using 0.6 M KCL and determined by the dextran-coated charcoal method. ER and AR levels were smaller in BPH plasma membranes (PM) than in Pca cases. For functions 3, 4, 6, the ER values in PCa were 25-38% less with regard to BPH ER values. Whereas in PCa, AR values obtained in all fractions were higher when compared to BPH AR values. In benign prostatic hypertrophy and prostatic cancer, ER and AR levels were significantly higher in the nuclear fraction. In the nuclear fraction, ER and AR levels in BPH and PCa were significantly different. The subcellular distribution of AR and ER in BPH and PCa constitutes a reservation mechanism and processing a receptors for their continued growth.

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Prostatic disorders are accompanied by extensive but poorly understood modifications of the cells and surrounding extracellular matrix. In this study, we examined the distribution of the elastic system fibers in prostatic disorders compared to normal tissue. Sections of prostatic transurethral resections and/or radical prostatectomies were examined after staining with hematoxylin-eosin plus fluorescence microscopy and after Weigert's staining for elastic fibers. Transmission electron microscopy was used to examine the ultrastructure of tissues from radical prostatectomy. A concentric fibrous extracellular matrix and smooth muscle cells were observed surrounding normal acini. The elastic fibers were thin and inconspicuous. In benign prostatic hyperplasia (BPH) the elastic components were of variable thickness and formed a three-dimensional network at the base of the epithelium. Conversely, increased variability in the elastic fiber distribution was observed in adenocarcinomas, depending on the tumor grade. In adenocarcinomas with little differentiation, in some hyperplasic acini, and in the stroma adjacent to tumoral mass, ruptured and residual elastic fibers indicative of matrix degradation or remodeling were seen. In more undifferentiated tumors, a pre-elastic network, perhaps indicative of a new extracellular matrix microenvironment was seen. These results indicate that prostate cancer cell invasion involves extensive remodeling of the fibers of the elastic system.

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Con el fin de definir la frecuencia y las características morfológicas de los adenocarcinomas de bajo grado que fueron confundidos con proliferaciones glandulares benignas, revisamos retrospectivamente 135 biopsias con carcinoma prostática. Tres biopsias (2.2 por ciento) mostraron adenocarcinomas de bajo grado en campos aislados que semejaban glándulas hiperplásicas en algunos campos histológicos y adenosis prostática en otros. Estas tres biopsias mostraron retrospectivamente características del adenocarcinoma prostático originado en la zona de transición. Algunos criterios de malignidad como el patrón infiltrante, los núcleos y nucléolos prominentes fueron observados aisladamente. No se identificaron secreciones basófilas intraluminales, cristaloides, células neoplásicas aisladas en el estroma ni mitosis en ningún caso. Concluímos que el análisis detallado de las características arquitecturales y citológicas de las proliferaciones glandulares prostáticas es necesario ya que el adenocarcinoma de bajo grado se puede encontrar esporádicamante como patrón histológico único en las biopsias por punción semejando lesiones glandulares benignas

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