Changes in keratin expression during the development of benign prostatic hyperplasia

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.