PReferentially Expressed Antigen in MElanoma (PRAME): preliminary communication on a translational tool able to early detect Oral Malignant Melanoma (OMM)

Abstract

Oral malignant melanoma (OMM) has a prevalence less than 1% of all melanomas and it commonly develops on the oral mucosa following a slow and unspecific transformation of unstable melanocytic lesions, often resulting in a diagnostic delay. The marker PReferentially Expressed Antigen in MElanoma (PRAME) seems to be a valid tool to investigate the biological and histological nature of cutaneous melanocytic lesions, but to date its use to characterize pigmented lesions in the oral cavity is largely unexplored. The aim of this study was to create preliminary knowledge on the PRAME expression in OMM, and to compare its expression respect to other dysplastic pigmented lesions of the oral cavity. Interestingly, PRAME has been demonstrated to be reliable in the clinical conditions investigated in our pilot study; in fact, it has clearly differentiated the cases of Melanoma, which showed diffuse and intense positivity (score 6+/7+) to PRAME, from the other melanocytic nevi, which resulted to be mainly negative to PRAME. This means a better differential diagnosis, a reliable early diagnosis and a proper clinical/surgical management of the oncological lesions. In conclusion, PRAME can be a valid qualitative marker for differential diagnosis, not only in cutaneous melanomas, but also in malignant melanoma of the entire head and neck area.

Tumor antigen PRAME is a potential therapeutic target of p53 activation in melanoma cells

“…Elevated PRAME expression is associated with poor outcomes in neuroblastoma and breast cancer ( 4 , 5 ). Recent immunohistochemical analysis revealed an increased expression of PRAME in primary and metastatic melanoma compared to normal nevi ( 6 - 8 ). The tumor promoting activity of PRAME was discovered via its depletion in xenograft mouse tumor models ( 9 - 11 ).…”

PRAME expression in melanoma is negatively regulated by TET2-mediated DNA hydroxymethylation

“…Preferentially Expressed Antigen in Melanoma (PRAME) has recently emerged as a candidate diagnostic biomarker that can be detected using standard immunohistochemistry (1)(2)(3)(4). Studies have shown immunostains for PRAME to represent a means of ancillary histopathology testing with high sensitivity and specificity for melanoma diagnosis, including ambiguous melanocytic neoplasms (1,5,6) and rare subtypes of melanoma (7)(8)(9)(10). This specificity arises because PRAME, a membrane-bound antigen, is not typically expressed in normal cells except for the testis (11,12).…”