Co-expression of Bmi1 and EZH2 as an independent poor prognostic factor in esophageal squamous cell carcinoma.

Bmi1 polycomb ring finger oncogene (Bmi1) and the enhancer of zeste homolog 2 (EZH2) are members of polycomb repressive complex (PRC) 1 and PRC2, respectively. PRC1 represses tumor suppressor genes such as p16INK4a and p14ARF in a PRC2-dependent manner. There have been few studies on Bmi1 or EZH2 expression in esophageal squamous cell carcinoma (ESCC). We investigated Bmi1 and EZH2 expression in 164 cases of ESCCs using immunohistochemistry, and evaluated the correlation with clinicopathologic features and their prognostic significance. Bmi1 and EZH2 were more highly expressed in tumor than in adjacent normal tissue (p<0.001). High expression of Bmi1 or EZH2 alone was not correlated with any clinicopathologic parameter and did not influence the prognosis. However, the group with high expression of both Bmi1 and EZH2 showed the poorest prognosis in overall survival (p=0.027) and disease-free survival (p=0.007). Also, it was an independent prognostic factor in overall survival (p=0.047). High expression of both Bmi1 and EZH2, not each alone, is an independent poor prognostic factor in ESCCs, supporting the repression of tumor suppressor gene by Bmi1 in an EZH2-dependent manner. This result suggests that both Bmi1 and EZH2, not each alone, could be potent candidates of new target therapy in ESCCs.