Expression of Cancer Stem Cell Markers Aldh1 and Ezh2 Are Increased in Triple Negative Breast Cancers
Jabed Iqbal, Kah Weng Lau, Aye Aye Thike, Syed S Ahmed, Puay Hoon Tan. Singapore General Hospital, Singapore, Singapore
Background: Breast carcinomas lacking expression of ER, PR, and HER2 (triple-negative breast carcinomas or TNBC) are characterized by aggressive behavior, distinct pattern of metastasis, and lack of targeted therapy. In this study we sought to evaluate the presence of cancer stem cell (CSC)-related markers in this group of cancers. CSCs are pluripotent tumor-initiating cells believed to be responsible for treatment failures and recurrences. We assessed the expression of CSC-related markers ALDH1 and EZH2 in triple negative breast cancers, investigating their association with clinicopathological features and outcome.
Design: Clinicopathological data were obtained from 131 triple negative breast cancers and 114 hormone-positive invasive breast cancers diagnosed between 2001 and 2008. Tissue microarray was constructed and immunohistochemistry for ALDH1 and EZH2 was performed using the streptavidin-biotin method. Intensity and proportion of tumor cells stained were assessed. Molecular subtype was based on immunophenotype of ER/PR/Her2. Follow-up information was obtained from case-notes. Disease free survival (DFS) and overall survival (OS) were defined as time from diagnosis to recurrence or death respectively. Cytoplasmic expression of ALDH1 and nuclear expression of EZH2 were evaluated. P values less than 0.05 were considered statistically significant.
Results: Tumour cells exhibited cytoplasmic expression of ALDH1 in 32% of TNBC cases while increased EZH2 expression was noted in 79% of TNBCs. EZH2 expression was highest in the basal-like breast cancer subgroup (83%). Luminal B subtype showed highest expression of ALDH1 (30%). Tumour cell expression did not correlate with any of the clinicopathologic parameters. Increased expression of either biomarker showed non-statistically significant trend of poor DFS in invasive ductal carcinoma but not in triple negative breast cancer patients.
Conclusions: In this study (1) EZH2 expression is increased in triple negative breast cancers/basal-like breast cancers indicating association with aggressive tumor behavior (2) DFS is worse in patients with increased expression of either CSC marker ALDH1 or EZH2. Further studies of CSC markers in the context of TNBC are warranted to identify new chemotherapeutic targets.
Tuesday, March 5, 2013 9:30 AM
Poster Session III # 23, Tuesday Morning