Expression of Two Stem Cell Markers (ALDH1 and Notch1) in Inflammatory Breast Carcinoma.
Jeff F Wang, Ping Liu, Yun Gong. The University of Texas MD Anderson Cancer Center, Houston
Background: Inflammatory breast cancer (IBC) is a rare but the most lethal form of breast carcinoma. Despite the current use of multimodality treatment, the clinical outcome of IBC patients is poor. Studies have shown that tumors arising from cancer stem cells (CSCs) are associated with drug resistance, tumor recurrence and aggressiveness. Whether dysregulation of CSCs has been implicated in IBC biology remains unclear. The aim of this study was to examine the expression of two stem cell markers, ALDH1 and Notch1, in IBC.
Design: Tissue microarray samples obtained from 75 surgically removed IBCs between September 1994 and August 2004 were immunohistochemically stained with ALDH1 and Notch1. Patients' information, tumor characteristics, and routine biomarkers were retrospectively reviewed. Positive ALDH1 status was defined as >1% of cancer cells showing cytoplasmic staining with at least moderate intensity. High expression of Notch1 was defined as >20% of cancer cells showing cytoplasmic and/or nuclear staining with at least moderate intensity. The expression status was correlated with overall survival (OS), and other pathologic variables.
Results: Patient age ranged from 23 to 75 years (median, 49 years). All patients received chemotherapy and 38% also received hormonal therapy. Median follow-up time was 3.51 years, and by the time of analysis, 44 patients had died. Median OS was 3.87 years (95% CI, 2.22, 8.79). The 5-year OS rate was 43.4%. Positive ALDH1 expression was found in 32.4% (24/74) tumors, and high expression of Notch1 was found in 42.5% (31/73) tumors. Univariate analysis of OS revealed no statistically significant association between positive ALDH1 expression and OS (P = 0.21) or between high expression of Notch1 and OS (P = 0.61). Furthermore, no significant association was found between the status of either marker and other clinicopathologic variables (age, race, nodal status, histologic type, lymphovascular invasion, nuclear grade, ER, PR, and HER2 status). ER and triple-negative status were significantly associated with OS in univariate analysis, and ER status remained an independent predictor of poor OS in multivariate analysis.
Conclusions: In this cohort of IBC patients, expression of ALDH1 and Notch1 did not significantly predict OS and did not correlate with other clinicopathologic variables, failing to confirm the significant role of stem cells in IBC biology. Further study with other stem cell markers is required to elucidate this issue.
Tuesday, March 1, 2011 1:00 PM
Poster Session IV # 8, Tuesday Afternoon