EZH2 Expression in Triple Negative Breast Carcinoma.
Yaser Hussein, Sudeshna Bandyopadhyay, Bassam Albashiti, Amro Almradi, Zeina Nahleh, Tarek Jazaerly, Hayan Jaratli, Rouba Ali-Fehmi. Wayne State University, Detroit, MI; Karmanos Cancer Institute, Detroit, MI; Detoit Medical Center, Detroit, MI
Background: The Polycomb Group Protein EZH2 is a transcriptional repressor involved in cell cycle regulation and has been linked to aggressive breast cancer and is being evaluated as a possible target therapy. Triple-negative (ER, PR, and Her-2 negative) breast carcinomas (TN) have aggressive clinical behavior and lack the benefit of targeted therapy. In this study, we investigated the expression of EZH2 in TN compared to non-TN breast carcinomas
Design: Tissue microarrays were constructed with 261 consecutive invasive breast carcinomas diagnosed at our institution over three years period with a median follow-up of 42 months. Immunohistochemistry for EZH2, CK5/6, EGFR and P53 was performed using standard procedures. EZH2 nuclear staining was scored based on intensity (0-3+) and it was categorized into low and high expression. The results were correlated with clinico-pathological variables and patient's outcome. Data was statistically analyzed using Chi-square or Fisher's exact tests, and survival was calculated by the Kaplan-Meier method
Results: Among the 261 cases, 57 (21%) cases were categorized as TN, and 204 (79%) as non-TN. High expression of EZH2 was detected in 87 (33%) cases, and it was strongly associated with a TN phenotype (p<0.0001) compared to all other non-TN tumors. High EZH2 was noted in 41 out of 57 (72%) of TN versus 46 out of 204 (22%) of non-TN tumors. Increased EZH2 expression also significantly correlated with younger age (mean age 54 years, p=0.008), higher grade (p=0.04), and high P53 expression (p=0.006). However, no correlation was observed with race, tumor size, lymph node status, and EGFR and CK5/6 expression. Survival analyses demonstrated that high EZH2 patients compared to those with low EZH2, had a trend towards poorer overall survival (68% vs 80%; p=0.07).
Conclusions: Our results show that high EZH2 expression is significantly associated with TN breast carcinoma and might be a potential therapeutic target for this aggressive subgroup of breast cancer, which warrants further investigations.
Monday, February 28, 2011 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 36, Monday Morning