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Changed lineage composition is an early event in breast carcinogenesis
Heidi N Hilton1, Silke Kantimm, J Dinny Graham
1Westmead Institute for Cancer Research, Sydney Medical School - Westmead, University of Sydney at Westmead Millennium Institute, Westmead, New South Wales, Australia. heidi.hilton@sydney.edu.au
Histology and Histopathology
|April 16, 2013
Summary
Changes in the proportion of luminal and myoepithelial cells in breast tissue correlate with increased proliferation and are early events in breast cancer. This finding may help identify premalignant lesions at higher risk for progression.
Area of Science:
- Human breast tissue biology
- Cellular composition in carcinogenesis
- Epithelial cell dynamics
Background:
- The human breast epithelium comprises luminal and myoepithelial cells, crucial for normal development.
- Altered proportions of these cells, particularly loss of myoepithelial cells, characterize breast cancer progression.
- The early events driving these cellular composition changes in carcinogenesis are poorly understood.
Purpose of the Study:
- To investigate the relationship between luminal and myoepithelial cell proportions and proliferation in normal and pre-invasive breast lesions.
- To determine if changes in cell type composition are an early event in breast carcinogenesis.
- To explore the potential of myoepithelial cell proportion as an indicator of malignant progression risk.
Main Methods:
- Quantification of luminal and myoepithelial cell proportions in normal, proliferative disease without atypia (PDWA), columnar cell lesions (CCL), atypical ductal hyperplasia (ADH), and ductal carcinoma in situ (DCIS) breast tissues.
- Correlation of cell lineage composition with proliferation markers within these lesions.
Main Results:
- A significant correlation was observed between altered luminal and myoepithelial cell proportions and increased cellular proliferation.
- These changes in lineage composition represent one of the earliest events identified in breast carcinogenesis.
- The relative proportion of myoepithelial cells compared to luminal cells may serve as an early indicator of progression risk.
Conclusions:
- Changes in the relative abundance of luminal and myoepithelial cells are linked to increased proliferation and occur early in breast carcinogenesis.
- Myoepithelial cell presence is critical for distinguishing invasive from non-invasive tumors.
- The ratio of myoepithelial to luminal cells shows potential as a biomarker for identifying premalignant lesions with a higher risk of progressing to invasive breast disease.
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