Membranous Expression of Activated Ezrin/Radixin/Moesin (ERM) Protein Is Positively Linked to Triple Negative Breast Cancer.
Sonal Varma, Andrew Day, Jamaica Cass, Victoria Hoskin, Blerta Sartova, Hannah Mak, Leda Raptis, Yolanda Madarnas, Sandip Sengupta, Bruce Elliott. Queen's University and Kingston General Hospital, Kingston, ON, Canada; Cancer Research Institute, Kingston, ON, Canada
Background: The cytoskeletal crosslinker protein, ezrin, a member of the ezrin/radixin/moesin (ERM) family, is expressed at the apical membrane in non-neoplastic breast lobules, but shows strong cytoplasmic expression in invasive breast cancers. Recently, another ERM family member, moesin, has been shown to be a distinguishing marker of triple negative (ER/PR/Her2 -ve) breast cancers (Int J Oncol. 34:983-93, 2009). However, we expect that the activated forms of ezrin and/or moesin may hold the potential for better predictive power. The focus of this report is an examination of expression and localization of activated/ phosphorylated ERM proteins in a cohort of human breast cancer.
Design: Using a triplicate core TMA of formalin-fixed tissue, we investigated 63 primary invasive breast cancers including 16% triple negative cases from women under 50 years of age. Immunohistochemistry was performed with antibody specific for pTERM, which shares epitope specificity with ezrin pT567 and moesin pT558, and for total ezrin and moesin proteins. Other clinico-pathological biomarkers (ER, PR, Her2, and p53) were also assessed. The stains were analyzed by two independent evaluators with resolution of discordant cases by a senior Pathologist. Cases were dichotomized according to triple negative versus all other cancer subtypes. A two-sided exact Fisher test was used to assess association of biomarkers with each category.
Results: pTERM showed continuous membranous staining in 19% (12/63) of breast cancer cases, compared to tight apical expression in breast lobules from 20 normal reduction mammoplasty specimens. A statistically significant association of pTERM with the triple negative breast cancer cases compared to all other cancer subtypes was observed. In particular, the prevalence of triple negative breast cancer was 42% and 10% in the pTERM positive and negative cases, respectively (p<0.017). Expression of total ezrin and moesin proteins and their co-localization with pTERM are currently being assessed.
Conclusions: We found unique association of membranous pTERM staining in a sub-population of triple negative human breast cancers. Since pTERM represents phosphorylated forms of both ezrin and moesin, our findings suggest that presence of activated states of these two ERM proteins may be a distinguishing feature of triple negative breast cancers.
Monday, February 28, 2011 1:00 PM
Poster Session II # 78, Monday Afternoon