Standardized Computer-Assisted Analysis of PRAME Immunoreactivity in Dysplastic Nevi and Superficial Spreading Melanomas

Int J Mol Sci. 2023 Mar 28;24(7):6388. doi: 10.3390/ijms24076388.

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.

Keywords: PRAME; computer-assisted analysis; dysplastic nevus; immunohistochemistry; melanoma.

MeSH terms

  • Antigens, Neoplasm / analysis
  • Diagnosis, Differential
  • Dysplastic Nevus Syndrome* / metabolism
  • Dysplastic Nevus Syndrome* / pathology
  • Humans
  • Male
  • Melanoma* / metabolism
  • Melanoma, Cutaneous Malignant
  • Nevus* / pathology
  • Skin Neoplasms* / pathology
  • Transcription Factors

Substances

  • Transcription Factors
  • Antigens, Neoplasm
  • PRAME protein, human

Grants and funding

This research received no external funding.