Comparison of S100A8 and PRAME as biomarkers for distinguishing melanoma from melanocytic naevus: a case–control analysis

Background S100A8 is a melanoma biomarker expressed in the melanoma-associated epidermal keratinocytes, but its diagnostic utility has not been compared with other biomarkers, including PRAME. Objectives To compare the utility of S100A8 and PRAME immunohistochemistry (IHC) in the differential diagnosis of melanoma and naevi in a case–control study. Methods A previously described cohort of 209 melanomas (case samples) and naevi (control samples) dual-immunostained for S100A8 and PRAME were included. For S100A8, previously reported scores indicating the proportion of tumour-associated epidermis stained (0=inde-terminate; 1=0–4%; 2=5–25%; 3=26–50%; 4=51–75%; 5= >75%) were utilized. PRAME IHC was reviewed by at least two reviewers and a consensus score assigned, with score indicating the proportion of tumour stained (0=indeterminate; 1=0%; 2=1–50%; 3= >50%). A positive test was defined as>50% staining. Results The area under the receiver operating characteristic curves for S100A8 (0.833) and PRAME (0.874) were not significantly different from each other (P=0.22). The diagnostic sensitivity and specificity were 42.4% [95% confidence interval (CI) 32.6–52.8%] and 98.2% (95% CI 93.6–99.8%) for S100A8, and 79.8% (95% CI 70.5–87.2%) and 87.3% (95% CI 79.6–92.9%) for PRAME, respectively. A combined test requiring both S100A8 and PRAME IHC positivity had a sensitivity of 39.4% (95% CI 29.7–49.7%) and specificity of 99.1% (95% CI 95.0–100.0%). Conclusions S100A8 and PRAME have utility in the diagnostic workup of melanoma, with S100A8 being more specific and PRAME being more sensitive when using this threshold. Our findings suggest that these two immunohistochemical markers may favourably complement one another to improve the detection of melanoma.