Differential Localization of EZRIN Expression in Normal and Neoplastic Mammary Tissue
C-H Chen, JA Chapman, A Rajput, H Mak, A Perry, H Feilotter, S SenGupta, BE Elliott. Queen's University, Kingston, ON, Canada; Cancer Research Institute, Kingston, ON, Canada
Background: The cytoskeletal plasma membrane cross-linker protein EZRIN is required for polarity of normal breast epithelium. Interestingly, loss of EZRIN function inhibits metastasis with little effect on primary growth of breast carcinoma cells in a xenograft model (Elliott et al., BCR 7:R365-73, 2005). Our goal was to examine the role of EZRIN and other associated signaling markers in a cohort of primary invasive breast cancers from premenopausal women and to explore if they are correlated with established prognostic factors.
Design: Using a triplicate core TMA of formalin-fixed tissue, we investigated sixty-two primary invasive breast cancers from women under 49 years of age. Immunohistochemistry was performed on the TMA for PAN-EZRIN and its modulators (E-CADHERIN, MET, SRC, STAT5), cell cycle/apoptosis regulators (BCL2, CYCLIN D1, P53), HER2/neu, ER and PR. The percentage of positive cells and staining intensity were scored by two independent evaluators with resolution of discordant cases by a senior Pathologist. The statistical analysis included Pearson and Spearman correlation coefficients.
Results: Forty-four infiltrating ductal and lobular carcinomas were analyzed. About half of invasive carcinomas (54.5%) displayed diffuse cytoplasmic PAN-EZRIN staining whereas the remaining half showed absence of staining. PAN-EZRIN expression was limited to the apical membrane in normal mammoplasty tissue (8%). Neither cytoplasmic nor membranous PAN-EZRIN was significantly associated with tumor size, nodal status, ER, PR and HER/neu expression (p>0.10).
Conclusions: We found unique localization of EZRIN staining in a sub-population of breast cancers. The fact that EZRIN plays a key role in cell adhesion, migration and division coupled with our finding that EZRIN staining did not correlate with established prognostic factors makes it tempting to speculate that EZRIN staining pattern may be an independent prognostic factor (Supported by Queen's Pathology Clinical Trust and CBCRA).
Monday, March 9, 2009 1:00 PM
Poster Session II # 48, Monday Afternoon