Publication in Human Pathology

Increased Expression of EZH2 in Merkel Cell Carcinoma Is Associated with Disease Progression and Poorer Prognosis

Kelly L. Harms, MD, PhD

, 

Heather Chubb, MS

, 

Lili Zhao, PhD

, 

Douglas R. Fullen, MD

, 

Christopher K. Bichakjian, MD

, 

Timothy M. Johnson, MD

, 

Shannon Carskadon, MS

, 

Nallasivam Palanisamy, PhD

, 

Paul W. Harms, MD, PhDCorrespondence information about the author MD, PhD Paul W. HarmEmail the author MD, PhD Paul W. Harms

DOI: http://dx.doi.org/10.1016/j.humpath.2017.07.009

Highlights

• •EZH2 is a histone methyltransferase that affects tumorigenesis by epigenetic gene silencing.
• •We found strong/moderate EZH2 immunohistochemical expression in 54% of Merkel cell carcinomas.
• •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.

Summary

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.

http://www.humanpathol.com/article/S0046-8177(17)30259-9/fulltext