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Background:  Enhancer of zeste homolog 2 (EZH2), a polycomb group protein that regulates the cell cycle, has recently been implicated in the progression of several human cancers. We sought to determine the pattern of EZH2 expression in benign and malignant melanocytic tumors to see if EZH2 might play a role in melanoma pathogenesis and progression.

Methods:  We identified and reviewed 11 compound nevi, 13 dysplastic nevi, 13 Spitz nevi, 9 in situ melanomas, 10 non-metastatic invasive melanomas and 19 melanomas metastatic to lymph nodes from the University of Michigan pathology archives. Sections immunostained with anti-EZH2 antibody were scored independently and blindly for staining intensity on a scale of 1–4 by three dermatopathologists. Results were analyzed and compared statistically.

Results:  We observed an incremental increase in EZH2 expression from benign nevi to melanoma: scores of 1.18 and 1.08 for ordinary and dysplastic nevi, 1.7 and 1.78 for Spitz nevi and in situ melanoma, and 1.9 and 3.0 for invasive and metastatic melanoma, respectively. EZH2 expression for metastatic melanoma was significantly higher compared with invasive and in situ melanoma and benign nevi (p ≤ 0.01).

Conclusions:  EZH2 protein levels increase incrementally from benign nevi to melanoma, which suggests that EZH2 may play a role in the pathogenesis and progression of melanoma.