1. ¹Institute of Pathology, University of Münster, Münster
2. ²Institute of Pathology, Philipps University of Marburg, Marburg, Germany
3. ³National Expert & Training Centre for Breast Cancer Screening, Academisch Ziekenhuis Nijmegen, Nijmegen
4. ⁴Department of Pathology, Free University Hospital, Amsterdam, The Netherlands
5. ⁵Pathology Department, University College Dublin, Mater Hospital, Dublin, Ireland
6. ⁶Institute of Clinical Chemistry and Laboratory Medicine, Münster, Germany
7. ⁷Department of Medicine B and Central Ultrastructure Research Unit, Interdisciplinary Center of Clinical Research, University of Münster, Münster, Germany

Correspondence: Dr. Werner Boecker, Professor of Pathology, Gerhard Domagk-Institute of Pathology, Domagkstrasse 17, D-48149 Münster, Germany. E-mail: boeckew@uni-muenster.de

Received 29 December 2001.

Abstract

Breast biology and pathology are currently shaped by the two-cell concept that recognizes only glandular and myoepithelial cells. In the present study, we have visualized a previously unidentified cell population within the epithelial compartment of the breast, which displays the phenotypic characteristics of a committed stem cell.

Immunofluorescence double labeling with digital image processing and Western blotting were applied to normal breast tissue as well as to noninvasive and invasive breast cancers using antibodies to basal cytokeratin 5 (Ck5), glandular cytokeratins 8/18 (Ck8/18/19), and smooth muscle -actin (SMA) as markers for myoepithelial cells (SMA).

A distinct population of cells was identified that expressed Ck5 in the absence of Ck8/18/19 or SMA. These cells differentiate toward glandular epithelial or myoepithelial Ck5-negative end cells passing through either Ck5/Ck8/18/19 or Ck5/SMA-positive intermediates. Our experiments clearly demonstrate a precursor or committed stem cell function of the Ck5-positive cell that is responsible for regeneration of the human adult breast epithelium. However, the observation that the vast majority of breast cancers display the glandular epithelial immunophenotype strongly suggests that the neoplastic cells derive from a late stage of the glandular epithelial differentiation pathway. The significance of this new cell biological model is that it might serve as a tool to unravel the regulatory mechanisms that govern regeneration and abnormal proliferation of breast epithelium at the cellular level.