EZH2 upregulation correlates with tumor invasiveness, proliferation, and angiogenesis in human pituitary adenomas

- EZH2 and MMP-14 in pituitary adenomas are upregulated on transcriptional and translational levels.
- EZH2 and MMP-14 are especially upregulated in pituitary invasive adenomas.
- EZH2 upregulation correlated with invasive behavior, MVD, Ki-67 LI, and MMP-14 protein expression.
- EZH2 could serve as a potential diagnostic marker for invasive pituitary adenomas.
- These results may also have treatment implications for invasive pituitary adenomas.

SummaryEnhancer of zeste homolog 2 (EZH2) is a critical component of the polycomb repressive complex 2, which epigenetically represses genes involved in tumorigenesis and is highly expressed in tumors. However, no studies have investigated EZH2 expression and its clinical significance in human pituitary adenomas (PAs). Therefore, we examined the expression pattern of EZH2 in PAs and studied the correlations between protein expression and invasiveness, proliferation, angiogenesis, hormone functioning, and some other factors. We measured EZH2 and MMP-14 protein and EZH2 mRNA expression in 62 samples of PAs by immunohistochemistry staining and quantitative real-time polymerase chain reaction and correlated protein expression relative to clinicopathologic features. The immunopositive rate of EZH2 was 88.7% (55/62). The extent of expression was associated with invasiveness, microvessel density, and proliferation (Ki-67 index). Moreover, EZH2 expression correlated with MMP-14 expression. We did not find any correlation between EZH2 overexpression and hormone-secreting function or patient age or sex. The quantitative real-time polymerase chain reaction analysis revealed that the amount of EZH2 mRNA was significantly higher in invasive than in noninvasive adenomas. This is the first report to describe EZH2 overexpression in human PAs, especially invasive adenomas. Thus, EZH2 is a potentially useful diagnostic marker and pharmacotherapeutic target for invasive PAs.