PRAME Expression in Melanocytic Tumors

Abstract

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.

Diffuse PRAME expression is highly specific for malignant melanoma in the distinction from clear cell sarcoma

“…The sensitivity of diffuse PRAME expression for MM in our cohort is consistent with the findings of Lezcano et al 4 Given the rarity of CCS, our study is limited by the small number of these cases. Through several observations, some investigators conclude that the loss of 5-hmC is because of downregulation of the enzymatic conversion from 5-mC.…”

“…3 With the identification of this biomarker, efforts to produce a reliable immunohistochemical stain developed and subsequent studies have reported that 5-hmC immunohistochemistry is a useful diagnostic tool in evaluating various melanocytic lesions. [4][5][6] However, there are only few studies examining expression of 5-hmC in spitzoid lesions. Those that do, have observed that…”

The immune microenvironment and expression of PD‐L1, PD‐1, PRAME and MHC I in salivary duct carcinoma

“…The following two parameters were documented for PRAME immunohistochemistry: (i) the staining pattern in TCs (cytoplasmic and/or nuclear); and (ii) the percentage of positive TCs (number of PRAME‐positive TCs/total number of TCs). Immunohistochemical analysis of PRAME was performed as described previously . PRAME immunopositivity was defined as any immunolabelling within the tumour.…”

“…Immunohistochemical analysis of PRAME was performed as described previously. 26 PRAME immunopositivity was defined as any immunolabelling within the tumour. Finally, the percentage of TCs (number of positive TCs/total number of TCs) showing membranous immunopositivity of MHC I was recorded and divided into three categories: positive (≥75% of TCs), heterogeneous (25-74% of TCs), and negative (<25% of TCs).…”

PRAME expression in melanocytic proliferations with intermediate histopathologic or spitzoid features

“…Recent studies by Lezcano et al characterized PRAME immunohistochemistry in a variety of melanocytic tumors, including benign melanocytic nevi, primary and metastatic melanoma, melanoma in situ, nodal nevi, and other benign melanocytic proliferations. 14,15 This valuable work highlighted the utility of PRAME immunohistochemistry in melanoma diagnosis via examination of largely histopathologically unequivocal benign and malignant melanocytic proliferations.…”