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

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.

Standardized Computer-Assisted Analysis of 5-hmC Immunoreactivity in Dysplastic Nevi and Superficial Spreading Melanomas

“…According to our data, epidermal expression has a higher significance in the context of the classification of melanocytic lesions. This has also been observed for other immunohistochemical markers [6,26]. Thus, intraepidermal melanocytes-considering subcorneal keratinocytes having a modest 5-hmC expression-should especially be carefully analyzed for 5-hmC expression to facilitate melanoma diagnosis in addition to morphologic features and potentially further immunohistochemical markers.…”

“…However, the performance of ROCAUC < 0.8 (epidermal ROCAUC = 0.79, entire lesion ROCAUC = 0.76) lacks diagnostic accuracy compared to other markers such as PRAME. We evaluated PRAME in DN and SSM and presented ROCAUC values of >0.87 [6]. According to this data, we suggested that a high PRAME expression of more than 100 cells/mm 2 is a strong indicator for melanoma, with a specificity of >87%, which is in comparison more reliable than 5-hmC [6].…”

“…We evaluated PRAME in DN and SSM and presented ROCAUC values of >0.87 [6]. According to this data, we suggested that a high PRAME expression of more than 100 cells/mm 2 is a strong indicator for melanoma, with a specificity of >87%, which is in comparison more reliable than 5-hmC [6]. These findings are in line with Rawson et al [7], who investigated a manual score of PRAME, 5-hmC, and p53 expression in tissue microarrays of 53 benign nevi (including 27 dysplastic nevi) and 280 invasive cutaneous melanomas including a variety of subtypes.…”

“…Further IHC markers have been established to aid in the differential diagnosis. Notably, expression of preferentially expressed antigen in melanoma (PRAME) and p53 (also a helpful marker for desmoplastic melanoma) are significantly higher in melanomas than in nevi [5][6][7]. On the other hand, 5-hydroxymethylcytosine (5-hmC) shows an intense immunoreactivity in benign nevus cells, whereas it is increasingly lost in dysplastic melanocytic nevi (DN) and frequently absent in melanomas [8,9].…”

Exploring the analysis capabilities and clinical application potential of the Claude 3 Opus in different dermatologic images: the development of a large-scale multimodal model to assist in dermatology clinical practice (Preprint)

“…The specific scoring criteria are detailed in Supplementary Table 2. The scoring criteria were established based on image descriptions from the selected textbook and a literature review on dermatopathology and dermoscopy images [25][26][27][28][29][30][31][32][33][34][35][36][37] . Two highly experienced dermatology experts with over 10 years of practice have reviewed and revised the scoring criteria.…”