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.
"Most investigators report that almost every cell in primary cultures derived from normal tissues expresses these basal cytokeratins (Brawer et al. 1986, Gao et al. 2001). Proliferation is also confined to the basal cells of normal tissues (McNeal et al. 1995, Kyprianou et al. 1996) and, similarly, primary cultures of normal prostatic epithelial cells are proliferative. "
[Show abstract][Hide abstract] ABSTRACT: This review focuses on primary cultures of human prostatic epithelial cells and their applications as models of normal and malignant biological behavior. Current abilities to culture cells from normal tissues, from premalignant dysplastic lesions (prostatic intraepithelial neoplasia), from primary adenocarcinomas, and from metastases are described. Evidence for representation of the interrelated cells of the normal prostatic epithelium--stem cells, basal epithelial cells, secretory epithelial cells, transit amplifying cells and neuroendocrine cells--in primary cultures is presented. Comparisons between normal and cancer-derived primary cultures are made regarding biological activities relevant to carcinogenesis, such as proliferation, apoptosis, differentiation, senescence, adhesion, migration, invasion, steroid hormone metabolism, other metabolic pathways and angiogenesis. Analyses of tumor suppressor activity, differential gene expression and cytogenetics in primary cultures have revealed changes relevant to prostate cancer progression. Preclinical studies with primary cultures have provided information useful for designing new strategies for chemoprevention, chemotherapy, cytotoxin therapy, radiation therapy, gene therapy and imaging. While the behavior of normal primary cultures is often used as a basis for comparison with established, immortal prostate cancer cell lines, the most informative studies are performed with donor-matched pairs of normal and malignant primary cultures, grown under identical conditions. Challenges that remain to be addressed if the full potential of primary cultures as a model system is to be realized include isolation, culture and characterization of stem cells, improved methodology to induce or maintain a fully differentiated, androgen-responsive phenotype, and identification of cell surface antigens or other markers with which to purify pure populations of live cancer or premalignant cells apart from non-malignant epithelial cells prior to culture.
Endocrine Related Cancer 04/2005; 12(1):19-47. DOI:10.1677/erc.1.00795 · 4.81 Impact Factor
[Show abstract][Hide abstract] 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.
[Show abstract][Hide abstract] ABSTRACT: To evaluate the role of androgens in the pathogenesis of prostatic dysplasia, we compared the localization of androgen receptor (AR) in proliferative and nonproliferative cells in normal and dysplastic acini. Basal cells, the only proliferating cells identified in normal acini, contained AR mRNA but lacked an immunodetectable receptor. Both AR mRNA and immunodetectable receptor were present, however, in secretory and stromal cells. Androgen receptor localization in dysplastic lesions was identical to normal but here the proliferative marker Ki-67 was found in both basal and secretory cells. Our findings suggest that androgens do not directly initiate the division of basal cells, the putative precursors of secretory cells. Instead, the hormone may act through its fully translated receptor to mainly mediate the differentiation of secretory cells. The presence of both AR and Ki-67 in dysplastic secretory cells may indicate an abnormal direct androgen-mediated proliferation in this compartment. This is consistent with previous evidence that secretory cell differentiation is impaired in dysplasia.
The Prostate 10/1996; 29(3):137-45. DOI:10.1002/1097-0045(199609)29:33.0.CO;2-Z · 3.57 Impact Factor
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