PRAME Updated: Diagnostic, Prognostic, and Therapeutic Role in Skin Cancer

Abstract

Preferentially Expressed Antigen in Melanoma (PRAME), a member of the cancer/testis antigen family, is central to the field of skin cancer diagnostics and therapeutics. As a nuclear receptor and transcriptional regulator, PRAME plays a critical role in inhibiting retinoic acid signalling, which is essential for cell differentiation and proliferation. Its aberrant overexpression in various malignancies, particularly cutaneous melanoma, is associated with more aggressive tumour phenotypes, positioning PRAME as both a diagnostic and prognostic marker. In melanoma, PRAME is typically highly expressed, in contrast to its weak or absent expression in benign nevi, thereby improving the accuracy of differential diagnoses. The diagnostic value of PRAME extends to various lesions. It is significantly expressed in uveal melanoma, correlating to an increased risk of metastasis. In acral melanomas, especially those with histopathological ambiguity, PRAME helps to improve diagnostic accuracy. However, its expression in spitzoid and ungual melanocytic lesions is inconsistent and requires a comprehensive approach for an accurate assessment. In soft tissue sarcomas, PRAME may be particularly helpful in differentiating melanoma from clear cell sarcoma, an important distinction due to their similar histological appearance but different treatment approaches and prognosis, or in detecting dedifferentiated and undifferentiated melanomas. In non-melanoma skin cancers such as basal cell carcinoma, squamous cell carcinoma, and Merkel cell carcinoma, the variable expression of PRAME can lead to diagnostic complexity. Despite these challenges, the potential of PRAME as a therapeutic target in melanoma is significant. Emerging immunotherapies, including T-cell-based therapies and vaccines targeting PRAME, are being investigated to exploit its cancer-specific expression. Ongoing research into the molecular role and mechanism of action of PRAME in skin cancer continues to open new avenues in both diagnostics and therapeutics, with the potential to transform the management of melanoma and related skin cancers.

Misdiagnosis and Clinical Insights into Acral Amelanotic Melanoma—A Systematic Review

“…Clinicians should be alert to lesions that do not resolve, such as warts and ulcers, as these should prompt consideration of more serious conditions. Immunohistochemistry and the use of markers such as PRAME can be very helpful in distinguishing melanoma from other malignancies such as clear cell sarcoma [41,44]. However, despite the interesting results, the conclusions of this review must be tempered by the limitations discussed above.…”

“…The differentiation of AAM from sarcomas requires careful clinical evaluation, supported by histological and immunohistochemical analysis [40,42]. In this case, the use of PRAME as an immunohistochemical marker could be a valuable diagnostic aid; indeed, PRAME, which is expressed in melanoma but not in most sarcomas, could be an important discriminatory tool, improving the diagnostic accuracy of AAM [40][41][42][43][44]. Alternatively, traditional genetic studies may be very useful in the differential diagnosis between these two neoplasms [40,42].…”

To explore the potential diagnostic and prognostic value of Golgi related genes in prostate cancer

“…The AUC values for the prediction of 1-year, 3-year and 5-year OS were 0.67, 0.71 and 0.70, respectively, indicating high reliability and accuracy.In addition, the high risk group had signi cantly lower OS than the low risk group. The three genes we screened to construct the model were MUC6, PRAME and VGF.Recent studies have shown that MUC6 expression is a preferred prognostic marker for invasive mucous adenocarcinoma of the lung [26].Preferentially Expressed Antigen in Melanoma (PRAME), a member of the cancer/testis antigen family, is central to the eld of skin cancer diagnostics and therapeutics [27].VGF:A prospective biomarker and therapeutic target for neuroendocrine and nervous system disorders [28].Studies on GARGs laid the foundation for PCa immunotherapy. PCa expresses a variety of tumor-speci c antigens recognized by T cells, and the growth rate of PCa cells is relatively slow.…”

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

“…The tumor promoting activity of PRAME was discovered via its depletion in xenograft mouse tumor models ( 9 - 11 ). Therefore, targeting PRAME, either by exploiting its immunogenic or oncogenic potential, has been proposed as a strategy for tumor therapy ( 12 , 13 ). PRAME expression is upregulated by promoter DNA hypomethylation ( 14 , 15 ) and is stimulated by cooperation with myeloid zinc finger 1 ( 16 ).…”