Immunohistochemical analysis of Bcl-2 and Bax expression in relation to cell turnover and epithelial differentiation markers in the non-lactating human mammary gland epithelium

The expression of the apoptosis-related proteins Bcl-2 and Bar was investig ated by immunohistochemistry in the normal non-lactating human mammary glan d in relation to cell proliferation and apoptosis. In order to characterize individual Bax/Bcl-2-immunoreactive cells, the epithelial markers cytokera tin 14 and 19 and the macrophage marker CD 68 were used. Secretory-like dif ferentiation of epithelial cells was characterized by histochemistry and le ctin staining of surface glycoconjugates. Cell proliferation was exclusivel y found in glandular epithelial cells with broad contact to the ductular lu men, whereas nuclei with apoptosis-related DNA fragmentation were seen pred ominantly in basally located glandular epithelial cells and in myoepithelia l cells. Weak immunoreactivity for Bcl-2 and Bar was present throughout all epithelia, suggesting a balance between pro- and antiapoptotic effects in the majority of epithelial cells. However, specific cells showed a strong s taining for Bar or Bcl-2. The strongly Bcl-2-immunoreactive epithelial cell s were not identical with proliferating cells, but they resembled them in c onfiguration and in the luminal intraepithelial position. In contrast, the strongly Bar-positive epithelial cells had no or only a narrow contact to t he ductular lumen. The different patterns of Bax/Bcl-2 immunoreactivity in specific glandular epithelial cells suggest that there are also different g rades of susceptibility towards apoptotic stimuli in individual glandular e pithelial cells. We conclude that specific Bax/Bcl-2 expression patterns co uld reflect particular cell differentiation states, and that the strongly B cl-2-positive cells in part could represent epithelial stem cells.