Epigenetics Markers in Acral Lentiginous/Mucosal Melanoma: Expression of EZH2.
Elsa M Li-Ning-Tapia, Jonathan Curry, Peter Zhang, Victor G Prieto, Carlos A Torres-Cabala. UT-MD Anderson Cancer Center, Houston, TX
Background: Melanoma is a neoplasm with a complex pathogenesis and behavior. Molecular markers of outcome and the development of new therapies are needed. EZH2 is an enzyme involved in epigenetic changes through methylation of histones and participates in silencing cell cycle regulatory genes such as INK4A that encodes protein p16.
Epigenetic changes are important therapeutic targets, because they are potentially reversible. Acral lentiginous/mucosal melanomas (ALM/MuM) are rare variants of melanoma that likely evolve through molecular pathways different from the more common types of melanoma. The status of EZH2 has not been evaluated in ALM/MuM.
Design: Eighteen formalin- fixed, paraffin-embedded tissue blocks of melanoma from eighteen patients were retrieved from the files of UT-MD Anderson Cancer Center. The cases comprised: acral lentiginous melanoma (n=3); mucosal melanoma (n=7); superficial spreading melanoma (n=2); lentigo maligna (n=2); nodular melanoma (n=2); metastatic melanoma (n=2). Sections were obtained and stained. Immunohistochemistry for EZH2 (clone 6A10), p16 and MITF-1 was performed using standard avidin biotin methods. Percentage of area stained (< 10%, 10-50% and >50%) and intensity of staining (0 to 3+) were scored.
Results: Patients age ranged from 11 to 82 years old (mean age 60.6); the female to male ratio was 1:1. Sites of melanoma included: foot (n=3), conjunctiva (n=1), upper respiratory tract (n=2), rectal mucosa (n=3), urethra (n=1), back (n=1), neck (n=1), thigh (n=1), ear (n=1), lymph node (n=1), skin metastasis (n=1), head (n=1) and arm (n=1). Nuclear expression of EZH2 was observed in 53.3% of all melanoma cases (8/18). 66.6% (6/9) cases of ALM/MuM showed strong expression of EZH2. All ALM/MuM co-expressed p16 and MITF-1 by immunohistochemistry.
Conclusions: In our series, EZH2 was expressed in most cases of ALM/MuM. This novel marker is a potential target for therapy. To the best of our knowledge, this is the first time that the expression of EZH2 is assessed in ALM/MuM.
Tuesday, March 1, 2011 9:30 AM
Poster Session III # 114, Tuesday Morning