Original contributionIncreased expression of EZH2 in Merkel cell carcinoma is associated with disease progression and poorer prognosis

- EZH2 is a histone methyltransferase that affects tumorigenesis by epigenetic gene silencing.
- We found strong/moderate EZH2 immunohistochemical expression in 54% of MCCs.
- EZH2 is expressed at higher levels in nodal metastases compared to primary tumors.
- Weaker EZH2 expression in primary tumors correlated with improved prognosis.
- These findings suggest EZH2 may play a role in MCC progression.

SummaryEnhancer of zeste homolog 2 (EZH2) is a histone methyltransferase that affects tumorigenesis by epigenetic gene silencing. Merkel cell carcinoma (MCC) is a rare cutaneous neuroendocrine carcinoma that has a high risk of disease progression with nodal and distant metastases. Here, we evaluated EZH2 expression by immunohistochemistry in a cohort of 85 MCC tumors (29 primary tumors, 41 lymph node metastases, 13 in-transit metastases, and 2 distant metastases) with clinical follow-up. We show strong/moderate EZH2 expression in 54% of tumors. Importantly, weak expression of EZH2 in the primary tumor, but not nodal metastases, correlated with improved prognosis compared to moderate/strong EZH2 expression (5-year MCC-specific survival of 68% versus 22%, respectively, P = .024). In addition, EZH2 was expressed at higher levels in nodal metastases compared to primary tumors (P = .005). Our data demonstrate that EZH2 has prognostic value and may play an oncogenic role in MCC.