PRAME

PRAME (Preferentially expressed antigen in melanoma, CT130, MAPE (melanoma antigen preferentially expressed in tumors) or OIP4 (OPA-interacting protein 4) was initially identified as a tumor antigen, which could be recognized by human leukocyte antigen (HLA)-A24 restricted cytotoxic T lymphocytes in metastatic cutaneous melanoma. Based on its function, this gene has been recently renamed as PRAME nuclear receptor transcriptional regulator (GeneID: 23532).PRAME belongs to a group of cancer testis antigens (CTAs) that are predominately expressed in the normal testis, but as well in a variety of tumors, and are involved in immunity and reproduction. PRAME is part of PRAME family, group of over 20 distinct genes and 10 pseudogenes clustered on the human chromosome 1. PRAME gene is located on human chromo­some 22 (22q11.22), but it is known that mul­tiple mRNAs can be produced from the gene through the use of alternative transcription start sites and alternative splicing. The exact function of PRAME is unknown, but the protein interferes with retinoic acid receptor signalling and thus PRAME Inhibits RA-Induced differentiation, proliferation arrest, apoptosis and tissue homeostasis.PRAME has been classified as a testis-selective rather than a testis-restricted CTA, as low PRAME mRNA expression has been observed in endometrial, ovarian, and adrenal gland tissues in addition to the high expression observed in testes.

Around 83% of malignant melanomas and around 95% of metastatic melanoma
33-49% of desmoplastic melanomas
25-30% of benign or atypical Spitzoid lesions
10-15% of benign melanocytic tumors show weak positivity in minority of  nuclei (<75%)
100% of myxoid and round cell liposarcoma, around 70% of osteosarcoma,
100% squamous cell carcinoma of thymus and only in minority of cases of thymoma. 

40% acute myeloid leukemia (AML)  chronic myelogenous leukemia (CML), 30% acute lymphoblastic leukemia (ALL), 18 % in Hodgkins lymphoma.

Weak nuclear expression in cases of lobular and ductal NOS breast carcinoma in 25% respectively <35%. PRAME expression in <20% HER-2 positive breast carcinomas, triple negative cases are in general negative. Elevated PRAME expression in found an independent prognostic factor for reduced disease-free survival and overall survival in breast carcinoma patients.

Varying frequency of positive staining is also reported in of 40% renal cell carcinoma, non-small cell lung carcinoma (NSCLC) and neuroblastoma.

Clear cell sarcoma is reported to give consistently negative staining in contrast to malignant melanomas.

Diagnosis of primary and metastatic melanoma (especially in sentinel lymph node settings)
Differential diagnosis of melanoma (positive) versus nevi (negative)
Differential diagnosis clear cell sarcoma (negative) vs. malignant melanoma (positive)
Differential diagnosis squamous cell carcinoma of thymus vs. thymoma

At present testis, tonsil and adrenal are suggested as recommended positive and negative tissue controls for PRAME. In testis protocols must be calibrated to provide a weak to moderate, distinct nuclear staining reaction in about 30-50% of most germ cells, scattered germ cells based at basal lamina will show a moderate to strong nuclear staining reaction. Dispersed Leydig cells will typically show a weak membranus stainig reaction. In adrenal gland scattered cells in cortex will show a weak to moderate membranous staining reaction and focally also a nuclear staining reaction can be observed.  In tonsil virtually all lymphocytes must be negative and no staining should be seen.