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Standardized Computer-Assisted Analysis of PRAME Immunoreactivity in Dysplastic Nevi and Superficial Spreading
Elias A T Koch1,2, Michael Erdmann1,2, Carola Berking1,2
1Department of Dermatology, Uniklinikum Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), 91054 Erlangen, Germany.
Abstract:
PRAME (PReferentially expressed Antigen in MElanoma) is a cancer testis antigen that is frequently expressed in melanoma compared to benign melanocytic proliferations and nevi. However, the interpretation of the intensity and distribution of PRAME immunostaining is not standardized a lot, which makes interpretation difficult. PRAME-stained histological slides of superficial spreading melanomas (SSM) and dysplastic nevi (DN) were digitized and analyzed using the digital pathology and image platform QuPath. t-tests and ROC AUCs were performed with SPSS. A p-value of <0.05 was used for statistical significance, and a ROC AUC score of >0.8 was considered a good result. A cut-off score was defined in an evaluation cohort and subsequently analyzed in an independent validation cohort. In total, 81 PRAME-stained specimens were included. The evaluation cohort included 32 (50%) SSM and 32 (50%) DN, and the mean of PRAME-positive cells/mm2 for the entire lesion was 455.3 (SD 428.2) in SSM and 60.5 (SD 130.1; p < 0.001) in DN. The ROC AUC of PRAME-positive cells of the entire lesion was 0.866, and in the epidermis it was 0.901. The defined cut-off score to distinguish between DN and SSM was 97.67 cells/mm2. In the validation cohort, 16 out of 17 cases (94.1%) were correctly classified by the cut-off score. The computer-aided assessment of PRAME immunostaining is a useful tool in dermatopathology to distinguish between DN and SSM. Lesions with a moderate expression and indifferent morphologic features will remain a challenge for dermatopathologists.
Insights
PRAME immunostaining aids in distinguishing melanoma from nevi. Computer-aided analysis of PRAME-positive cells offers a reliable tool for dermatopathologists, improving diagnostic accuracy for melanoma.
Area of Science:
- Dermatopathology
- Oncology
- Digital Pathology
Background:
- PRAME (PReferentially expressed Antigen in MElanoma) is a cancer testis antigen.
- PRAME is frequently expressed in melanoma but its immunostaining interpretation lacks standardization.
- Distinguishing melanoma from nevi is critical for patient management.
Purpose of the Study:
- To develop and validate a computer-aided method for quantifying PRAME expression.
- To assess the utility of PRAME immunostaining in differentiating melanoma from dysplastic nevi.
- To establish a standardized diagnostic approach for PRAME in histopathology.
Main Methods:
- Digitization of PRAME-stained histological slides of melanoma and dysplastic nevi.
- Analysis using the QuPath digital pathology platform.
- Statistical analysis including t-tests and ROC AUCs with a defined cut-off score.
Main Results:
- A significant difference in PRAME-positive cells/mm² was observed between melanoma (455.3) and dysplastic nevi (60.5; p < 0.001).
- ROC AUC scores for PRAME-positive cells were 0.866 for the entire lesion and 0.901 for the epidermis.
- A cut-off score of 97.67 cells/mm² correctly classified 94.1% of cases in a validation cohort.
Conclusions:
- Computer-aided assessment of PRAME immunostaining is a valuable tool in dermatopathology.
- This method aids in distinguishing dysplastic nevi from melanoma.
- Challenging cases with moderate expression and ambiguous morphology require further investigation.
