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.

Keywords: Differential Diagnosis.; Early diagnosis; Oral Malignant Melanoma.

Figure 1

Examples of OMM that were strongly immunopositive for PRAME. (A) Histological features of hyperpigmented OMM of the hard palate in a patient with local advanced disease (Hematoxylin-Eosin, Original Magnification 4x, scale bar: 500 µm). (B) Another case of pigmented OMM of the gingiva: note the sheets of melanocytic neoplastic cells (Hematoxylin-Eosin, Original Magnification 10x, scale bar: 250 µm). (C) Photomicrograph corresponding to the case of (A) showing intense and widespread immunoexpression for PRAME (Immunostaining for PRAME, Original Magnification 4x, scale bar: 500 µm). (D) Immunohistochemical preparation of case (B) which also shows strong and widespread positivity of immunostaining for PRAME (Preparation for immunostaining for PRAME, Original Magnification 20x, scale bar: 100 µm).

Figure 2

(A) Example of benign nevus on oral mucosa: note the almost total negativity for PRAME immunostaining (Immunostaining for PRAME, Original Magnification 10x). (B) Representative picture of positive control of PRAME in a sebaceous gland (Immunostaining for PRAME, Original Magnification 10x).