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Updated: Aug 26, 2025
A Robust Discovery Platform for the Identification of Novel Mediators of Melanoma Metastasis
Published on: March 8, 2022
PRAME is a useful marker for the differential diagnosis of melanocytic tumours and histological mimics
Yan-Ping Chen1, Wen-Wen Zhang1, Ya-Ting Qiu1
1Department of Pathology, Clinical Oncology School of Fujian Medical University and Fujian Cancer Hospital, Fuzhou.
Aims:
Although the morphological assessment of melanoma is generally straightforward, diagnosis can be especially difficult when the significant morphological and immunohistochemical results overlap with those of benign and malignant melanocytic tumours and histological mimics. This study assessed the potential diagnostic utility of measuring PReferentially expressed Antigen in MElanoma (PRAME) immunohistochemically in naevi, melanomas and clear cell sarcomas (CCSs) in Chinese patients.
Methods:
We examined the immunohistochemical expression of PRAME in 317 melanocytic naevi, 178 primary melanomas, 72 metastatic melanomas and 19 CCSs and compared the sensitivity and specificity of PRAME immunohistochemistry (IHC) in the differential diagnosis of melanocytic tumours and histological mimics.
Results:
Of the 317 melanocytic naevi, 98.1%were completely negative for PRAME; six cases showed focal PRAME immunoreactivity in a minor population of lesional melanocytes. Diffuse nuclear immunoreactivity for PRAME was found in 89.9% of primary melanomas and 93.1% of metastatic melanomas. Regarding melanoma subtypes, PRAME was expressed in 100% of superficial spreading melanomas, 100% of melanomas arise in congenital naevus, 91.4% of nodular melanomas, 87.8% of acral lentigo melanomas, 80.0% of lentigo malignant melanomas, 60.0% of Spitz melanomas, 96.2% of mucosal melanomas and 80.0% of uveal melanomas. None of the two desmoplastic melanomas expressed PRAME. Of the 19 CCS cases, 89.5% were negative for PRAME and 10.5% showed focal weak PRAME immunoreactivity in a minor population of tumour cells.
Conclusions:
Our findings indicate that PRAME may be a useful marker to support a suspected diagnosis of melanoma. In addition, lack of PRAME expression is a valuable hint to CCS in a suspected case, and then molecular confirmation of the presence of EWSR1 rearrangement is necessary.
Insights
PReferentially expressed Antigen in MElanoma (PRAME) immunohistochemistry aids melanoma diagnosis. Negative PRAME expression suggests clear cell sarcoma, requiring molecular confirmation.
Area of Science:
- Oncology
- Dermatopathology
- Immunohistochemistry
Background:
- Melanoma diagnosis can be challenging due to overlapping features with benign melanocytic lesions and mimics.
- Immunohistochemistry plays a crucial role in differentiating complex skin lesions.
Purpose of the Study:
- To evaluate the diagnostic utility of PReferentially expressed Antigen in MElanoma (PRAME) immunohistochemistry in distinguishing melanocytic naevi, melanomas, and clear cell sarcomas (CCSs).
- To assess the sensitivity and specificity of PRAME expression in Chinese patients.
Main Methods:
- Immunohistochemical analysis of PRAME expression was performed on 317 melanocytic naevi, 178 primary melanomas, 72 metastatic melanomas, and 19 CCSs.
- Comparison of PRAME expression patterns across different lesion types.
Main Results:
- PRAME was negative in 98.1% of naevi, while 89.9% of primary and 93.1% of metastatic melanomas showed diffuse nuclear PRAME expression.
- PRAME expression varied among melanoma subtypes, with high positivity in superficial spreading and mucosal melanomas, but absent in desmoplastic melanomas.
- Most CCS cases (89.5%) were negative for PRAME, with some showing focal, weak immunoreactivity.
Conclusions:
- PRAME immunohistochemistry is a valuable marker supporting melanoma diagnosis.
- Lack of PRAME expression can indicate clear cell sarcoma, necessitating further molecular testing for EWSR1 rearrangement.
- PRAME aids in the differential diagnosis of melanocytic tumors and mimics.
