Cytokeratin 5/6 in normal human breast: lack of evidence for a stem cell phenotype

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Abstract
In recent studies, Böcker and colleagues described a population of cells in paraffin wax sections of normal human breast that express cytokeratins (CK) 5/6 without expression of CK8/18 or smooth muscle actin (SMA). They proposed that these represent stem cells that give rise to differentiated luminal and myoepithelial cells. The data have been used to generate a model for breast cancer progression and classification with associated implications for management of pre‐invasive disease. In this study, the expression of CK5/6, CK8/18, and SMA was investigated using multiple immunofluorescence on matched pairs of paraffin wax‐embedded and frozen breast specimens. The staining patterns reported previously in antigen‐retrieved paraffin wax‐embedded sections were confirmed but no CK5/6‐only cells were found in frozen sections of normal breast. There were cells with low levels of CK8/18 expression in frozen sections that may correspond to the CK8/18 ‘negative’ cells seen in paraffin wax sections. This study brings into question the previously described profile of breast ‘stem cells’ based on CK5/6 staining and hence the breast cancer progression model and classification based on this phenotype. Copyright © 2004 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.