Increased expression of EZH2 in Merkel cell carcinoma is associated with disease progression and poorer prognosis.

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Human pathology


Enhancer 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.

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Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Carcinoma, Merkel Cell; Disease Progression; Disease-Free Survival; Enhancer of Zeste Homolog 2 Protein; Female; Humans; Immunohistochemistry; Lymphatic Metastasis; Male; Middle Aged; Predictive Value of Tests; Proportional Hazards Models; Retrospective Studies; Risk Factors; Skin Neoplasms; Time Factors; Treatment Outcome; Up-Regulation

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