PRAME expression

Exposure to GSK343 or ATRA results in inhibition of cell proliferation and induction of cellular senescence, where GSK343 shows a dominant effect. The Figure was created with Biorender.com.

The PRAME has significance in discriminating the conjunctival malignant melanoma and pigmented nevus. It is a useful biomarker in the diagnosis of conjunctival malignant melanoma.

PRAME expression confirmed the existence of a late-onset oncogenic nevoid pathway that can be defined by histopathology. Subsequent meta-analysis data linked to the meta-analytic framework revealed that PRAME is an epigenetic surrogate antigen expressed because of repression of retinoic acid receptor signaling, preventing ligand-induced retinoic acid cellular differentiation, growth arrest, and apoptosis, and promoting melanoma growth and survival for melanomas. PRAME is only a single antigen within a highly complex dynamic framework that governs nevoid oncogenesis. Significantly, the retinoic acid/retinoic acid receptor complex has been shown to modulate the immunosuppressive arm of regulatory T cells underpinning immune tolerance and is pertinent to the broad framework but is not linked to PRAME expression in this arm.

Then, the present results can suggest that elevated PRAME and Ki-67 expression are associated with poor overall survival in cutaneous melanoma; however, in multivariate analysis, only the Breslow thickness had a significant influence. These findings highlight the potential of PRAME and Ki-67 as prognostic markers, opening frontiers that could improve strategies for treating cutaneous melanoma.

Double staining of CD34 and PRAME revealed that PRAME-positive and CD34-positive areas did not overlap. This is the largest study to examine PRAME expression in FS-DFSP, and it confirmed the usefulness of PRAME in diagnosing this condition.

In conclusion, PRAME staining helps distinguish thin melanomas from dysplastic nevi. However, the threshold of positivity should be lowered in order not to miss thin melanomas.

Inhibition of poly(ADP-ribose) polymerase-1 (PARP-1) and PARP-2 in cells expressing PRAME could lead to potential therapeutic applications. Pathway enrichment analysis underscores the significance of PRAME and BAP1 in melanoma pathogenesis.

Although PRAME is expressed in normal sebaceous units, it appears less useful as diagnostic marker for PSC, especially in poorly differentiated tumors. In difficult cases, panels of IHC studies (adipophilin, Ber-EP4, and EMA) achieve a definitive diagnosis.

PRAME is a useful marker for the diagnosis of melanoma in cytology material, but it is less sensitive than SOX10. PRAME is also expressed in other nonmelanocytic tumors which limits its specificity.

However, histone acetylation may be one of the epigenetic mechanisms involved in PRAME regulation. Thus, the therapeutic combination of histone deacetylase inhibitors and PRAME immunotherapy merits further investigation.

Lesions not associated with DICER1 pathogenic variants also showed ER-positive stromal cells, including cystic pulmonary airway malformations, cystic renal dysplasia, and simple renal cysts in adult kidneys. ER expression in stromal cells is not a feature of DICER1 perturbation but rather is related to the presence of cystic components.

As the available data primarily stem from adult melanoma, and given the clinical and histological distinctions in pediatric melanomas, our understanding of PRAME expression in this specific patient group remains limited. The age-dependent low PRAME expression shown here constrains the use of this marker in pediatric melanoma and may also limit the use of immunotherapeutic strategies against PRAME in young patients.