Expression of Stem Cell Marker (ALDH1) Correlates with Aggressive Molecular Subtypes of Breast Cancer
S Nofech-Mozes, J Zubovits, H Kahn, J Wong, RS Saad, A Seth, M Yaffe, C Peressotti, G Clarke, WM Hanna. Sunnybrook Health Sciences Centre, Toronto, Canada
Background: Data from preclinical models have recently identified ALDH1 (Aldehyde dehydrogenase 1) as a marker of cancer stem cells. The aim of this study was to assess the level of ALDH1 expression within the molecular subtypes of breast cancer that correlates with prognosis and response to adjuvant treatment.
Design: ALDH1 expression was examined in 121 invasive ductal carcinomas (114 primary and 7 locally recurrent tumors). Immunohistochemistry (BD Bioscience, 1:1000) was applied to tissue microarray from 105 cases (arrayed in triplicates) and 16 full section slides of invasive breast carcinoma accessioned between 2007-2009. For the purpose of this study only strong cytoplasmic stain was considered positive while nuclear or weak stain was considered nonspecific. Results were scored in 4-tiered system based on the percentage of positive cells (0= no stain, 1= 1-10%, 2=11-50%, 3=51-100%). Data on tumor characteristics was retrieved from the pathology report. Associations between ALDH1 status, estrogen and progesterone receptors (ER, PR) and HER2/neu status as well as pertinent pathological parameters were assessed with the χ2-test.
Results: There were 75 ER+/HER2/neu-, 23 HER2/neu+ and 23 triple negative (TN) cases. The proportion of tumours expressing ALDH1 in >10% was significantly higher in HER2/neu+ cases compared with ER+/HER2/neu- (39% vs 8% respectively, p=0.0092) and in TN when compared with ER+/HER2/neu- (26% vs 8% respectively, p=0.02). No significance difference was noted between the expression of ALDH1 expression in HER2/neu+ and TN tumors (p=0.34). ALDH1 expression in >10% of the cells in primary tumors did not correlate with patient age, tumour size, Nottingham grade 3, presence of in situ component, lymphovascular invasion or nodal status.
Conclusions: Our study showed that the proportion of tumors that express stem cell marker ALDH1 is significantly higher in aggressive types of breast cancers namely HER2/neu+ and TN subtypes.
Tuesday, March 23, 2010 11:45 AM
Platform Session: Section C, Tuesday Morning