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PRAME Expression in Melanocytic Tumors

Lezcano, Cecilia, MD*; Jungbluth, Achim A., MD*; Nehal, Kishwer S., MD; Hollmann, Travis J., MD, PhD*; Busam, Klaus J., MD*

The American Journal of Surgical Pathology: November 2018 - Volume 42 - Issue 11 - p 1456–1465
doi: 10.1097/PAS.0000000000001134
Original Articles

PRAME (PReferentially expressed Antigen in MElanoma) is a melanoma-associated antigen that was isolated by autologous T cells in a melanoma patient. While frequent PRAME mRNA expression is well documented in cutaneous and ocular melanomas, little is known about PRAME protein expression in melanocytic tumors. In this study we examined the immunohistochemical expression of PRAME in 400 melanocytic tumors, including 155 primary and 100 metastatic melanomas, and 145 melanocytic nevi. Diffuse nuclear immunoreactivity for PRAME was found in 87% of metastatic and 83.2% of primary melanomas. Among melanoma subtypes, PRAME was diffusely expressed in 94.4% of acral melanomas, 92.5% of superficial spreading melanomas, 90% of nodular melanomas, 88.6% of lentigo maligna melanomas, and 35% of desmoplastic melanomas. When in situ and nondesmoplastic invasive melanoma components were present, PRAME expression was seen in both. Of the 140 cutaneous melanocytic nevi, 86.4% were completely negative for PRAME. Immunoreactivity for PRAME was seen, albeit usually only in a minor subpopulation of lesional melanocytes, in 13.6% of cutaneous nevi, including dysplastic nevi, common acquired nevi, traumatized/recurrent nevi, and Spitz nevi. Rare isolated junctional melanocytes with immunoreactivity for PRAME were also seen in solar lentigines and benign nonlesional skin. Our results suggest that immunohistochemical analysis for PRAME expression may be useful for diagnostic purposes to support a suspected diagnosis of melanoma. It may also be valuable for margin assessment of a known PRAME-positive melanoma, but its expression in nevi, solar lentigines, and benign nonlesional skin can represent a pitfall and merits further investigations to better assess the potential clinical utility of this marker.

Departments of *Pathology

Medicine, Memorial Sloan Kettering Cancer, New York, NY

Conflicts of Interest and Source of Funding: Supported in part by the Cancer Center Support Grant of the National Institutes of Health/National Cancer Institute under award number P30CA008748. The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article.

Correspondence: Klaus J. Busam, MD, Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY 10065 (e-mail: busamk@mskcc.org).

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