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[Cancer Research 64, 3037-3045, May 1, 2004]
© 2004 American Association for Cancer Research

Regular Articles

Expression Profiling of Purified Normal Human Luminal and Myoepithelial Breast Cells

Identification of Novel Prognostic Markers for Breast Cancer

Chris Jones1, Alan Mackay2, Anita Grigoriadis2, Antonio Cossu3, Jorge S. Reis-Filho1, Laura Fulford1,4, Tim Dexter1, Susan Davies2, Karen Bulmer1, Emily Ford1, Suzanne Parry1, Mario Budroni5, Giuseppe Palmieri6, A. Munro Neville2, Michael J. O’Hare2 and Sunil R. Lakhani1,7

1 The Breakthrough Toby Robins Breast Cancer Research Centre, Institute of Cancer Research, London, United Kingdom; 2 Ludwig Institute for Cancer Research/University College London Breast Cancer Laboratory, University College London, London, United Kingdom; 3 Istituto di Anatomia Patologica, Università di Sassari, Italy; 4 Ludwig Institute for Cancer Research, University College London, United Kingdom; 5 Servizio Epidemiologia, Sassari, Italy; 6 Istituto di Chimica Biomolecolare, Alghero, Italy; and 7 The Royal Marsden Hospital, London, United Kingdom

The normal duct-lobular system of the breast is lined by two epithelial cell types, inner luminal secretory cells and outer contractile myoepithelial cells. We have generated comprehensive expression profiles of the two normal cell types, using immunomagnetic cell separation and gene expression microarray analysis. The cell-type specificity was confirmed at the protein level by immunohistochemistry in normal breast tissue. New prognostic markers for survival were identified when the luminal- and myoepithelial-specific molecules were evaluated on breast tumor tissue microarrays. Nuclear expression of luminal epithelial marker galectin 3 correlated with a shorter overall survival in these patients, and the expression of SPARC (osteonectin), a myoepithelial marker, was an independent marker of poor prognosis in breast cancers as a whole. These data provide a framework for the interpretation of breast cancer molecular profiling experiments, the identification of potential new diagnostic markers, and development of novel indicators of prognosis.




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Copyright © 2004 by the American Association for Cancer Research.