title: Cytokeratin 5/6 in normal human breast: lack of evidence for a stem cell phenotype.
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.
authors.affiliation: Breakthrough Toby Robins Breast Cancer Research Centre, Institute of Cancer Research, London, UK.
authors.forename: Catherine L
authors.initials: CL
authors.lastname: Clarke
authors.forename: Jennifer
authors.initials: J
authors.lastname: Sandle
authors.forename: Suzanne C
authors.initials: SC
authors.lastname: Parry
authors.forename: Jorge S
authors.initials: JS
authors.lastname: Reis-Filho
authors.forename: Michael J
authors.initials: MJ
authors.lastname: O'Hare
authors.forename: Sunil R
authors.initials: SR
authors.lastname: Lakhani
mesh_terms: D000199:Actins / Q000032:analysis; D001940:Breast / Q000737:chemistry* / Q000166:cytology; D001943:Breast Neoplasms / Q000473:pathology; D002471:Cell Transformation, Neoplastic; D018450:Disease Progression; D004847:Epithelial Cells / Q000737:chemistry / Q000166:cytology; D005260:Female; D005455:Fluorescent Antibody Technique / Q000379:methods; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D053538:Keratin-18; D053555:Keratin-5; D053533:Keratin-8; D007633:Keratins / Q000032:analysis*; D009130:Muscle, Smooth / Q000737:chemistry; D009363:Neoplasm Proteins / Q000032:analysis; D010641:Phenotype; D013234:Stem Cells / Q000737:chemistry
chemical_list: D000199:Actins; C488421:KRT18 protein, human; C503940:KRT5 protein, human; C426203:KRT8 protein, human; D053538:Keratin-18; D053555:Keratin-5; D053533:Keratin-8; D009363:Neoplasm Proteins; D007633:Keratins