Cell proliferation in dysplasia of the prostate: analysis by PCNA immunostaining.
ABSTRACT Patterns of cell proliferation in the prostate were compared between benign epithelium and dysplasia. Proliferating cell nuclear antigen (PCNA) immunostaining was used to quantitate proliferation, and basal cells were tallied separately from secretory cells with the aid of keratin immunostaining. Using a novel technique, absolute cell densities (cells/mm) were determined and used to calculate growth fractions. In benign epithelium, 83% of PCNA+ cells were basal cells, while only 7% of PCNA+ cells in dysplasia were basal cells and there was a clear separation between groups. This dramatic shift of the proliferative compartment to the secretory cells in dysplasia was accompanied only by a moderate increase in overall secretory cell density and moderate reduction in basal cell density, but these ranges overlapped those of benign epithelium. The median PCNA+ secretory cell "growth fraction" was 0.12% in benign epithelium and 1.06% in dysplasia. The findings presented give further support to the concept that dysplasia represents an evolutionary stage in the malignant transformation of prostatic epithelium. The patterns of change in PCNA immunostaining may reflect certain aspects of the biologic nature of malignant transformation.
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ABSTRACT: Dimethylarsinic acid (DMA(V) ), the major urinary metabolite of inorganic arsenic, is a urinary bladder carcinogen and bladder tumor promoter in adult rats. Increased urothelial cellular proliferation has been considered as an earlier phenotype in DMA(V) -induced bladder carcinogenesis. The present study examined the ultrastructural changes of bladder epithelial cells and expressions of proliferation factors, as well as the secretion of inflammatory cytokines in rats exposed to DMA(V) for 10 weeks by transmission electron microscopy (TEM), qRT-PCR, immunohistochemical staining and ELISA methods. The results showed that DMA(V) administered in the drinking water produced urothelial cytotoxicity and ultrastructural changes in rats. PCNA, cyclin D1 and COX-2 mRNA expressions and immunoreactivities were elevated in bladder urothelium. In addition, 200 ppm DMA(V) treatment increased the transforming growth factor-beta 1 (TGF-β1) secretion and decreased tumor necrosis factor-alpha (TNF)-α level in the urine of rats. These data suggest that chronic inflammation, bladder epithelium lesions and proliferation might be the basic process of the chronic toxicity effects in DMA(V) -treated rats. Copyright © 2014 John Wiley & Sons, Ltd.Journal of Applied Toxicology 02/2015; 35(2). DOI:10.1002/jat.3001 · 3.17 Impact Factor
Article: Prostate Stem Cell CompartmentsAmerican Journal Of Pathology 09/1998; 153(3):911-919. DOI:10.1016/S0002-9440(10)65632-5 · 4.60 Impact Factor
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ABSTRACT: RESUMO A neoplasia intra-epitelial prostática (PIN) é uma lesão não-invasiva da próstata que apresenta anormalidades genéticas, perda de controle das funções celulares e características fenotípicas do câncer invasivo. Microscopicamente essa neoplasia consiste de alterações histo e citológicas no epitélio de revestimento ductal ou ácinos pré-existentes, exibindo geralmente distribuição multifocal. A lesão pode ser classificada em PIN de baixo (LGPIN) ou alto grau (HGPIN). Os aspectos morfológicos que incluem ruptura da camada de células basais, aumento da capacidade proliferativa epitelial e da densidade microvascular, sugerem que o HGPIN é um estágio intermediário de progressão do epitélio benigno a carcinoma. Palavras-chave: neoplasia intra-epitelial prostática (PIN), próstata, cão, imunoistoquímica. ABSTRACT Prostatic intraepithelial neoplasia (PIN) is a non-invasive prostatic lesion that shows genetic abnormalities, cellular functions changes and phenotypic invasive cancer pattern. Histopathological exam shows histo and cytological changes in pre existing ducts and acines, mostly in a multifocal way. The lesion can be classified as low grade PIN (LGPIN) or high grade PIN (HGPIN). Morphological aspects, including basal membrane rupture, higher proliferative index and micro vascular density are suggestive that HGPIN is an intermediate stage between normal epithelium and carcinoma.