Expression of the Stem Cell Markers ALDH1 and EZH2 in Triple Negative Invasive Breast Carcinomas
LP Kunju, K Toy, D Thomas, Y Ding, CG Kleer. University of Michigan, Ann Arbor, MI
Background: Markers associated with ER, PR and HER2/neu negative invasive breast carcinomas (triple negative, TN) may help in the diagnosis and treatment of these aggressive tumors. Emerging studies indicate that stem cells may be responsible for tumor initiation. There is no literature on expression of stem cell markers in TN carcinomas. We characterized ALDH1 and EZH2 expression in a cohort of uniformly treated TN patients and evaluated the ability of EZH2 to predict a TN phenotype.
Design: A tissue microaary was constructed with 52 invasive TN carcinomas. ALDH1 and EZH2 expression was evaluated using conventional immunohistochemistry (IHC) and AQUA analysis. By IHC, EZH2 was scored as 1 (negative), 2 (weak), 3 (moderate) and 4 (strong). Scores 1 and 2 were considered low, and scores 3 and 4 were considered high. ALDH1 was assessed as positive or negative in the epithelium and stroma, following published criteria. EZH2 expression was compared between TN and a cohort of non-TN tumors.
Results: EZH2 expression was nuclear. High EZH2 was strongly associated with a TN phenotype (p<0.0001) compared to all other non-TN tumors. High EZH2 expression was noted in 42 of 52 (81%) TN tumors and was significantly associated with high histological grade (p=0.0002). ALDH1 expression was cytoplasmic. Twelve of 52 (23%) TN tumors were positive for ALDH1 in the epithelial component while 32 (61%) showed ALDH1 in the stromal fibroblasts, which has not been previously reported. ALDH1 expression was not associated with tumor grade, size, angiolymphatic invasion or lymph node metastasis in TN carcinomas. However, when combined with high EZH2, both markers showed a very strong association with histological grade (p=0.0006) and tended to have larger size (p=0.06). We did not find a good correlation between expression of these markers by IHC and AQUA analysis.
Conclusions: High EZH2 expression predicts a TN phenotype in breast cancer, and identifies poorly differentiated tumors with high histological grade. ALDH1 is more commonly expressed by stromal cells than epithelial cells in TN carcinomas. Concordant high EZH2 and positive epithelial ALDH1 expression is associated with high histological grade and larger size in TN breast cancers. There is poor correlation between expression of these markers between immunohistochemistry and AQUA analysis, which warrants further investigation.
Monday, March 9, 2009 1:45 PM
Platform Session: Section B, Monday Afternoon