Xue Y, Smedts F, Umbas R, Aalders T W, Debruyne F M, de la Rosette J J, Schalken J A
Department of Urology, University of Hospital Nijmegen, The Netherlands.
Eur Urol. 1997;32(3):332-8.
The relationship between different types of epithelial cells in the prostate and the regulatory mechanism underlying benign prostatic hyperplasia (BPH) are still obscure as is the association between BPH and prostate carcinoma (PCa.) On the basis of keratin immunophenotyping, a subpopulation of cells in normal rat prostate and human PCa have been identified as candidates for the 'amplifying cell' in the stem cell model. In this model the basal cell is described as being associated with the stem cell. From this precursor an intermediate cell type develops which may differentiate into the luminal-type cell. In this study these different cell types are investigated in the development of isolated BPH and BPH associated with PCa, using monoclonal antibodies to intermediate filaments of the keratin class.
We immunohistochemically stained 64 snap-frozen human prostatic tissues, using monoclonal antibodies against keratin 14 (marker for putative 'stem cell'), keratin 18 (marker for putative 'transit cell'), and MAb RCK103 (marker for putative 'amplifying cell' or intermediate cell).
In basal cell hyperplasia, an atypical form of BPH, keratins previously associated with intermediate cells were frequently detected. Cells with this keratin phenotype were detected in the luminal compartment of BPH, and were more prevalent in BPH adjacent to PCa. This keratin expression pattern was similar to that of PCa.
On the basis of keratin phenotyping we demonstrated that large numbers of cells with the keratin expression pattern of so-called intermediate cells were identified in BPH associated with PCa, while in isolated BPH these cells were infrequently found. This supports the concept that BPH with intermediate phenotype may have premalignant potential. Furthermore this is suggestive of an etiologic relationship between the two diseases.
前列腺中不同类型上皮细胞之间的关系以及良性前列腺增生（BPH）的潜在调控机制仍不明确，BPH与前列腺癌（PCa）之间的关联亦是如此。基于角蛋白免疫表型分析，已在正常大鼠前列腺和人类PCa中鉴定出一群细胞作为干细胞模型中“扩增细胞”的候选细胞。在该模型中，基底细胞被描述为与干细胞相关。从这个前体细胞发育出一种中间细胞类型，其可能分化为管腔型细胞。在本研究中，使用针对角蛋白类中间丝的单克隆抗体，对孤立性BPH以及与PCa相关的BPH的发展过程中的这些不同细胞类型进行了研究。
我们使用针对角蛋白14（假定“干细胞”的标志物）、角蛋白18（假定“过渡细胞”的标志物）和单克隆抗体RCK103（假定“扩增细胞”或中间细胞的标志物）的单克隆抗体，对64例速冻人类前列腺组织进行了免疫组织化学染色。
在基底细胞增生（一种非典型的BPH形式）中，先前与中间细胞相关的角蛋白经常被检测到。具有这种角蛋白表型的细胞在BPH的管腔区被检测到，并且在与PCa相邻的BPH中更为普遍。这种角蛋白表达模式与PCa相似。
基于角蛋白表型分析，我们证明在与PCa相关的BPH中鉴定出大量具有所谓中间细胞角蛋白表达模式的细胞，而在孤立性BPH中很少发现这些细胞。这支持了具有中间表型的BPH可能具有癌前潜能的概念。此外，这暗示了这两种疾病之间的病因学关系。
