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EZH2 is a polycomb group protein that mediates repression of gene transcription at the chromatin level through its methyltransferase activity. EZH2 methylates histone H3 on lysine 27 (H3K27). EZH2 is overexpressed in many cancers and correlates with poorer prognosis in both prostate and breast cancer. However, the status of H3K27 methylation and its clinical effect in cancer patients has not been reported. We examined the expression of trimethylation of H3K27 (H3K27me3) by immunohistochemistry and its association with clinical features and prognosis in breast cancer. We also compared breast cancer with normal breast tissues for the expression of H3K27me3. We found that H3K27me3 expression was significantly lower in breast cancer than in normal tissues (62% in breast cancer vs 88% in normal breast tissue, p=0.001). H3K27me3 expression showed significant prognostic impact in breast cancer in univariate survival analyses. Patients with low expression of H3K27me3 had significantly shorter overall survival time when compared with those with high H3K27me3 expression. In a multivariate model, H3K27me3 expression was an independent prognostic value for overall survival in breast cancer. These results suggest that H3K27me3 expression is a prognostic indicator for clinical outcome in patients with breast cancer.

98th AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA