Cell proliferation in dysplasia of the prostate: analysis by PCNA immunostaining.
Department of Urology, Stanford University School of Medicine, California, USA. The Prostate
(Impact Factor: 3.57).
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.
Available from: Jayant K Rane
- "In contrast, a luminal progenitor cell population expressing telomerase could expand and give rise to terminally differentiated luminal cells, which do not replicate, maintaining a telomere length similar to that of the luminal progenitors. Our data is in agreement with both Bonkhoff et al  and McNeal et al  with respect to the existence of a proliferative basal compartment in which the potential luminal progenitors derived from basal SCs exhibit characteristics of both basal and luminal phenotypes, analogous to castration-resistant Nkx3.1-expressing cells in mice . The second implication of our model is that local inhibition of telomerase in BPH could be an alternative therapeutic strategy, as it will inhibit the proliferation both luminal and basal epithelial progenitors but perhaps not that of stromal cells. "
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ABSTRACT: Benign prostatic hyperplasia (BPH) treatments have changed little over many years and do not directly address the underlying cause. Because BPH is characterised by uncontrolled cell growth, the chromosomal telomeres should be eroded in the reported absence or low levels of telomerase activity, but this is not observed. We investigated the telomere biology of cell subpopulations from BPH patients undergoing transurethral resection of prostate (TURP). Measurement of TERC, TERT, and telomerase activity revealed that only the epithelial stem-like and progenitor fractions expressed high levels of telomerase activity (p <. 0.01) and individual enzyme components (p <. 0.01). Telomerase activity and TERT expression were not detected in stromal cells. Telomere length measurements reflected this activity, although the average telomere length of (telomerase-negative) luminal cells was equivalent to that of telomerase-expressing stem/progenitor cells. Immunohistochemical analysis of patient-derived BPH arrays identified distinct areas of luminal hyperproliferation, basal hyperproliferation, and basal-luminal hyperproliferation, suggesting that basal and luminal cells can proliferate independently of each other. We propose a separate lineage for the luminal and basal cell components in BPH. Patient summary: We unexpectedly found an enzyme called telomerase in the cells that maintain benign prostatic hyperplasia (BPH), suggesting that telomerase inhibitors could be used to alleviate BPH symptoms. In benign prostatic hyperplasia (BPH), a small population of basal cells expresses high levels of telomerase. Basal and luminal cells can proliferate independently, implying distinct basal and luminal lineages and suggesting that telomerase-blocking drugs could inhibit epithelial hyperproliferation in BPH.
Available from: erc.endocrinology-journals.org
- "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. "
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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.
Available from: Renee Laufer Amorim
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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.
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