Mills Ch3 Breast

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SECTION II : Breast

A

B

both luminal epithelial cells and myoepithelial cells (34). The relationship of these putative “progenitor” cells to mam- mary stem cells is an unresolved issue (34,35). However, it is clear that the cells with the characteristic features of stem cells (i.e., self-renewal and the ability to differentiate down different cell lineages to form all of the cell types found in the mature tissue) do exist in the breast. Mammary stem cells appear to be important in both breast development (36) and mammary carcinogenesis (35,37,38). Phenotypic fea- tures that have been associated with the mammary stem cell population include lack of expression of ER and progester- one receptor (PR), high expression of CD44, low or absent expression of CD24 and expression of aldehyde dehydroge- nase 1 (ALDH1) (38,39), although the most accurate com- bination of markers to reliably identify mammary stem cells is unresolved at this time. A basal lamina consisting of type IV collagen and laminin surrounds the mammary ducts, ductules, and acini (21,40). This basal lamina is present outside of the myoepithelial FIGURE 3.8  Extralobular duct ( A ) and lobule ( B ) immunostained for p63. The myoepithelial cells show strong nuclear reactivity, whereas the epi- thelial cell nuclei are negative. C: Double immunostain for smooth muscle actin (red cytoplasmic staining) and p63 (brown nuclear staining) high- light the myoepithelial cells around this mammary duct. Note the lack of staining of the epithelial cells for both p63 and smooth muscle actin.

C

expression is not seen in myoepithelial cells of the intra- lobular ductules and acini (32). Normal breast luminal epithelium is composed of cells in various states of differentiation as demonstrated by a panel of biomarkers that includes estrogen receptor (ER), androgen receptor, vitamin D receptor, low- and high- molecular–weight cytokeratins, and Ki67. Interestingly, each of these cell types appears to correspond to breast cancers with a similar immunophenotype, raising the possi- bility that breast tumors have phenotypes or differentiation states which correspond to those of normal cells, akin to that seen in hematologic malignancies (33). A third cell type dispersed irregularly throughout the ductal-lobular system expresses high—molecular-weight cytokeratins 5 and 14 in the absence of expression of mark- ers of differentiated luminal epithelial cells (such as low– molecular-weight cytokeratins) or myoepithelial cells (such as smooth muscle actin). These cells have been postulated to represent progenitor cells capable of differentiating into