Stem Cell Marker (ALDH1) Is a Strong Prognostic Factor in Breast Cancer.
Anna Plotkin, Sharon Nofech-Mozes, Steven A Narod, Ping Sun, Ellen Rawlinson, Wedad M Hanna. University of Toronto, ON, Canada
Background: Data from preclinical models have recently identified ALDH1 (Aldehyde dehydrogenase 1) as a marker of cancer stem cells. We have previously demonstrated that the proportion of tumors that express stem cell marker ALDH1 is significantly higher in aggressive types of breast cancers. The aim of this study is to examine ALDH1 as a prognostic marker in breast cancer.
Design: ALDH1 expression was examined in 1017 breast cancer cases from the Henrietta Banting database of well characterized cases with a mean follow up of 8.3 years, treated in a single institution. Immunohistochemistry (BD Bioscience, 1:1000) was applied to tissue microarray arrayed in triplicates. 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 3-tiered system based on the percentage of positive cells (negative= no stain, low = 1-50%, high high>50%). The association between ALDH1, and the standard prognostic factors, including age, tumor size, grade, nodal status, ER, PR, HER2 and Ki67 status was examined. Survival analyses to evaluate the outcome according to ALDH1 expression using univariate and multivariate models were done.
Results: ALDH1 immunohistochemistry revealed 275 negative, 680 ALDH1-low and 64 ALDH1-high cases. OS was significantly poorer in ALDH1-low and high cases when these groups were compared to ALDH1 negative cases (RR 1.34 (CI 1.01-1.78) and RR1.76 (CI 1.1-2.79) respectively). The difference in survival by ALDH1 expression persisted beyond 5 years (Figure 1). ALDH1 expression was significantly associated with size (p<0.0001), positive lymph nodes (p<0.0001), high grade (p=0.001), positive HER2 (p=0.001), ki67 (p=0.04), positive PR (p=0.04) but not with ER (p=0.21).
Conclusions: This is the largest single institution cohort that examined the prognostic significance of ALDH1. Our study demonstrates that ALDH1 is a robust prognostic factor in breast cancer and supports the biological rationale and hypothesis that expression of this stem cell marker is associated with poor overall survival in all subsets of breast cancer in this large data base.
Tuesday, March 1, 2011 1:00 PM
Poster Session IV # 6, Tuesday Afternoon