Abstract 1061: EZH2 expression in different subtypes of human breast cancer

Introduction: Cancer is characterized by aberrant patterns of expression of multiple genes believed to be due to not only genetic but also epigenetic changes. The epigenetic changes are communicated through chemical modifications, including modifications of histone proteins. For each histone, multiple histone-modifying enzymes have been discovered in mammals. We found that the expression of genes with histone modifications was highly predictable from the level of expression of the corresponding histone-modifying enzyme. Specifically, expression of genes displaying histone H3 K27 methylation was dependent on EZH2 expression. Method: We analyzed breast cancer tissue arrays for EZH2 expression. Tissue microarrays were constructed from 95 histologically confirmed breast cancer samples. To identify breast cancer subtypes, the tissues were evaluated for the expression of ER, PR, HER2, CK5/6 and EGFR. Staining with vimentin served as a control to monitor the quality of tissue fixation in archival tumors. Breast cancer subtypes were defined as luminal A (ER+ and/or PR+, HER2-), luminal B (ER+ and/or PR+, HER2+), basal-like (ER-, PR-, HER2-, CK5/6+, and/or EGFR+), HER2+/ER- (HER2+, ER-, PR-), and unclassified (negative for all five markers). EZH2 expression was measured by staining using an anti- EZH2 antibody (Invitrogen, cat. #18-7395). Staining quantification was performed independently by two pathologists. Results: The mean age of the patients was 56 years old (SD=15.6). 63.7% of the patients had estrogen receptor positive tumors, 50.6% had progesterone receptor positive tumors, and 21.2% had HER2+ tumors. The distribution of breast cancer subtypes is luminal A (58.9%), luminal B (6.3%), HER2+/ER- (4.2%), basal-like (28.5%), unclassified (2.1%). A majority of the patients had high grade tumors (46.0% grade II and 47.1% grade III). High EZH2 expression was associated with Her2+ and basal-like tumors (P