Expression profiling of purified normal human luminal and myoepithelial breast cells: identification of novel prognostic markers for breast cancer.
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.
Jones
Chris
C
The Breakthrough Toby Robins Breast Cancer Research Centre, Institute of Cancer Research, London, United Kingdom.
Mackay
Alan
A
Grigoriadis
Anita
A
Cossu
Antonio
A
Reis-Filho
Jorge S
JS
Fulford
Laura
L
Dexter
Tim
T
Davies
Susan
S
Bulmer
Karen
K
Ford
Emily
E
Parry
Suzanne
S
Budroni
Mario
M
Palmieri
Giuseppe
G
Neville
A Munro
AM
O'Hare
Michael J
MJ
Lakhani
Sunil R
SR
D001940:Breast / Q000166:cytology* / Q000378:metabolism / Q000502:physiology*; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D009367:Neoplasm Staging; D020411:Oligonucleotide Array Sequence Analysis; D015676:Osteonectin / Q000378:metabolism; D011379:Prognosis
D015676:Osteonectin