Preferentially Expressed Antigen in Melanoma Immunostaining in a Series of Melanocytic Neoplasms

Abstract

In their 2018 article, Lezcano et al [AJSP 2018(11):1456] show that diffuse tumor cell nuclear reactivity for Preferentially expressed Antigen in Melanoma (PRAME) is a feature of melanoma and that benign and atypical melanocytic tumors are PRAME negative or show only focal positivity for PRAME. We report our observations of PRAME staining in 253 melanocytic tumors. Tumors were classified by hematoxylin and eosin sections. The nuclear PRAME staining of neoplastic melanocytes in each case was categorized as absent, focally present, or diffusely present. The results were compared with those of Lezcano et al 105 of 134 (78%) melanocytic nevi were completely PRAME negative. Of the 29 PRAME-positive benign lesions, 28 exhibited focal but not diffuse positivity, including atypical (n = 11) and dysplastic nevi (n = 11). One of 11 Spitz nevi showed diffuse positivity (9%). Thirty-nine of 51 (76%) invasive melanomas, 41 of 50 (82%) melanoma in situ, and 15 of 18 (83%) metastatic melanomas were diffusely PRAME positive. Excluding desmoplastic melanomas, 39 of 49 (80%) primary melanomas were diffusely PRAME positive. Our findings of PRAME staining in melanocytic neoplasia are in general agreement with those of Lezcano et al. Diffuse PRAME reactivity in neoplastic melanocytes is a feature of malignancy and was only otherwise seen in 1 Spitz nevus. Caution is advised in interpretation of PRAME reactivity in melanocytic tumors of uncertain classification because melanoma arising in association with nevus and some atypical melanocytic tumors may show focal or incomplete PRAME staining. Routine histopathological findings, clinical information, PRAME staining, and judicious application of molecular studies are steps leading to accurate classification of melanocytic neoplasia.

PRAME expression in melanocytic lesions of the conjunctiva

“…Diffuse PRAME expression was found in 77 of 87 (88.5%) non‐desmoplastic invasive melanomas and only one of 145 (0.7%) melanocytic naevi 1 . These findings have been further supported in several studies 4–11 . Immunohistochemical analysis of PRAME expression has been shown to differentiate reliably between intranodal naevi and nodal metastatic melanomas, 4 to assist in distinguishing melanocyte populations in melanoma arising within naevi, 5 to be useful in evaluation of challenging melanocytic lesions 6,8,9 and in the assessment of surgical margins in lentigo maligna 10 …”

“…To the best of our knowledge, PRAME expression in conjunctival melanocytic lesions has so far been analysed in two studies, one including 70 conjunctival melanomas and 12 naevi, and another including 30 melanocytic lesions of different types (including only two invasive melanomas) 20,21 . As the utility of PRAME expression for separating malignant from benign melanocytic lesions may vary depending on the type and site of melanocytic lesions, data from cutaneous lesions cannot be directly applied to conjunctival melanocytic lesions 1,4–11 . Our aim was to analyse PRAME expression in a large number of different melanocytic lesions of the conjunctiva in order to test its utility in differentiating between conjunctival naevi, invasive or in‐situ melanomas or PAM.…”

PRAME protein expression in DICER1‐related tumours

“…PRAME is normally only expressed in testis, ovary, placenta, adrenal gland, and endometrium [ 22 , 23 ]. PRAME expression is best known in cutaneous melanoma [ 24 , 25 , 26 , 27 ] and uveal melanoma [ 28 ]. However, PRAME expression has also been documented in a wide variety of other malignancies, including non‐small cell lung cancer, squamous cell carcinoma of the head and neck, squamous cell carcinoma of the oesophagus, gastric carcinoma, hepatocellular carcinoma, breast carcinoma, renal cell carcinoma, urothelial bladder carcinoma, ovarian carcinoma, endometrial carcinoma, seminoma, various leukaemias, medulloblastoma, neuroblastoma, synovial sarcoma, myxoid liposarcoma, dedifferentiated liposarcoma, angiosarcoma, malignant peripheral nerve sheath tumour, and osteosarcoma [ 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 ].…”

“…PRAME expression is almost exclusively restricted to malignancies. A notable exception is expression (almost universally focal) in up to a quarter of benign melanocytic nevi [ 24 , 25 , 27 ].…”

Preferentially Expressed Antigen in Melanoma (PRAME) and Human Malignant Melanoma: A Retrospective Study

“…In this scenario, rising attention is being devoted to this marker, and new studies are being conducted in an attempt to increase experiences, report results, and find safer answers [ 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 ].…”