[104] ALDH1 is a useful marker of basalness in human breast cancer and its stem/progenitor cells.
Jolicoeur F, Garcia de la Fuente I, Gaboury L, Balicki D H
tel-Dieu du CHUM and Universit
de Montral, Montreal, QC, Canada
Background: The basal cell subtype is a particularly aggressive form of breast cancer. The molecular mechanisms which underlie the aggressive course of basal cell breast cancer, as well as its corresponding tumor markers are currently under intense study. In addition, there is increasing evidence that cancer stem/progenitor cells are integral to the formation and perpetuation of breast cancer. Together with their progenitors, cancer stem cells may determine the therapeutic outcome and the clinical course of cancer. The first isoform of aldehyde dehydrogenase (ALDH1) has recently been reported to be a marker of breast stem/progenitor cells. Thus, we undertook this study to determine whether the immunohistochemical detection of ALDH1 in fixed breast cancer tissues correlates with selected basal and luminal cell surface markers.
Methods: Formalin-fixed, paraffin-embedded specimens were studied in triplicate using tissue microarrays from 57 breast cancer patients. In addition to ALDH1 staining, each of the following markers were studied using immunohistochemistry (IHC) in each sample: ER, PR, HER-2, the basal cell markers EGFR/HER1, CK5, CK14, CK17, SMA, and the luminal cell markers CK19, and EMA.
Results: ALDH1 staining was performed using IHC and subsequently evaluated using the Quick score. The Quick score takes into account both the percentage of positive cells, as well as the corresponding staining intensity. Our results suggest that breast cancer samples expressing the triple negative phenotype (ER-, PR-, HER-2 negative) together with one or more basal cell markers (EGFR/HER1,CK5, CK14, CK17, SMA) are associated with an elevated Quick score for ALDH1 staining, when compared with samples lacking the expression of these markers.
Conclusions: As it has been demonstrated that IHC detection of ALDH1 detects stem/progenitor cells in fixed breast samples, our results suggest that an elevated Quick score is associated with the enrichment of IHC basal cell markers in these samples. We are currently focusing on a larger number of breast cancer samples so that correlations can be studied as a function of therapeutic outcome and overall survival of breast cancer patients.
Thursday, December 11, 2008 5:30 PM
Poster Discussion Session: Micro Environment and Stem Cells (5:30 PM-7:00 PM)