Characteristics of the MicroRNA-Processing Enzymes in Melanocytic Skin Lesions: Dicer and DGCR8 Are Potential Biomarkers for Primary Cutaneous Melanomas

Abstract

Primary cutaneous melanoma (PCM) is an aggressive skin cancer. Its physiopathology is a challenge with heterogeneous pathways involved. As such, microRNA-processing enzymes have been shown to be deregulated in cancer. The aim of this study was to characterise the expression profile of Dicer, Drosha, DGCR8 and PACT enzymes in melanocytic skin lesions. A total of 126 formalin-fixed paraffin-embedded samples, including 42 benign nevi, 42 dysplastic nevi and 42 PCM, were studied using tissue microarray and immunohistochemistry, which was graded based on the percentage of immunoreactive tumour cells (%IRC). Increased Dicer immunoexpression was found in PCM compared to benign nevi (p = 0.044) and increased DGCR8 immunoexpression was found in PCM compared to dysplastic and benign nevi (p = 0.000). For Drosha and PACT, only dysplastic nevi showed an increased expression (p = 0.011). A ROC curve cut-off of 80% IRC was used. For Dicer, the specificity for non-malignant cutaneous lesions (NMCL) was 98.8%, and sensitivity for PCM was 31.0%. The negative predictive value (NPV) was 98.6% and positive predictive value (PPV) was 34.7%. For DGCR8, the specificity for NMCL was 100%, and sensitivity for PCM was 31.0%. The NPV was 98.6% and PPV was 100%. All cases with positive Dicer and DGCR8 immunoexpression were melanomas. Dicer was increased in nodular histologic subtype (p = 0.011) and DGCR8 was higher in males (p = 0.005). Both Dicer and DGCR8 were increased in ulcerated PCM (p < 0.05). Dicer and DGCR8 play an important role in melanoma development with a potential use as diagnostic tools to differentiate PCM from other melanocytic skin lesions.