Increased expression of EZH2 in Merkel cell carcinoma is associated with disease progression and poorer prognosis.
Harms KL, Chubb H, Zhao L, Fullen DR, Bichakjian CK, Johnson TM, Carskadon S, Palanisamy N, and Harms PW. Increased expression of ezh2 in merkel cell carcinoma is associated with disease progression and poorer prognosis. Hum Pathol 2017; 67:78-84.
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.
Medical Subject Headings
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