Identification of Molecular Alterations Leading to Malignancy in Ductoscopically Procured Mammary Epithelial Cells
D Tran-Thanh, V Iakovlev, C Wang, V Wong, K Warren, DR McCready, S Boerner, N Miller, B Youngson, WL Leong, SJ Done. Toronto General Hospital, Toronto, ON, Canada; Ontario Cancer Institute, Toronto, ON, Canada; Princess Margaret Hospital, Toronto, ON, Canada
Background: Mammary ductoscopy is a new endoscopic technique that has the potential to allow the direct sampling and analysis of a pure population of mammary epithelial cells. We are taking advantage this new technique to obtain epithelial cells along tumor-containing mammary ducts. This will allow us to define a geographic map of the genetic alterations leading to malignancy in breast cancer.
Design: Our study population consists of women undergoing mastectomy for invasive breast cancer. Cytology samples are procured intraoperatively by mammary ductoscopy from ducts leading to the tumor, and ducts opposite the tumor. Immediately after removal of the breast, a set of snap-frozen tissue samples are harvested from the same regions as well as from the tumor mass. Cytology samples are depleted of contaminating macrophages using magnetic bead technology and the presence of malignant cells is confirmed by a cytopathologist. Tissue samples are examined histologically and microdissection performed on corresponding cryosections. Nucleic acids are extracted from all cytological and microdissected tissue samples. DNA and RNA are subjected to array CGH and gene expression array profiling, respectively.
Results: Twenty-one patients undergoing mastectomy have been recruited to date. Our results indicate that 80% (17/21) of patients had a successful ductoscopy/ductal lavage procedure. Malignant epithelial cells are present in 35% (6/17) of lavage samples on cytological analysis. Preliminary array CGH data shows an increasing number of genetic alterations in epithelial ductal cells going from the nipple towards the tumor. Furthermore, genetic abnormalities can be identified in ductal cells sampled close to the nipple in some patients.
Conclusions: Mammary ductoscopy is a useful technique for procuring epithelial cells from breast cancer patients. In at least one third of our cases, malignant epithelial cells were retrieved. Comparison of the genetic profile of these cytology samples with microdissected tissue samples obtained from the same regions of the duct system is enabling us to evaluate this new technique. This study will result in a better understanding of the geographic location of genetically abnormal cells within the breast.
Monday, March 9, 2009 9:30 AM
Poster Session I Stowell-Orbison/Autopsy Award # 68, Monday Morning