Multicenter prospective clinical trial of molecular genetic markers for non-invasive differential diagnosis of benign and malignant melanocytic skin lesions.

Abstract

e21581 Background: Improving the accuracy of non-invasive diagnosis of skin tumors is becoming an urgent problem, given the clear increase in the incidence of melanoma in many countries. Dermoscopy and examination by an experienced dermatologist can reduce the NNE to 5–10 per melanoma (M) detected, however, achieving even this, clearly suboptimal, rate requires a long specialist training. Methods: We report results of prospective nonrandomized trial evaluating sensitivity and specificity of RNA profiling of cytological samples from adhesive transparent patches (ATP) applied to skin lesions. Routine pathology reports were obtained for all surgery samples. RNA extracted from ATP specimens (N = 126) was tested for mRNA expression of PRAME and LINC00518 genes. GAPDH was used as a reference gene. Sample was considered marker-positive if either PRAME or LINC00518 expression was detected. Results: Between June 2021 and November 2021, 126 pts undegoing excisional biopsy of skin lesions were included in the study at 5 centers. On pathology, invasive M was detected in 49 (38.9%) patients (mean Breslow thickness was 2.41 mm [95%CI 1,44 to 3.37]), M in situ in 6 (4.8%), non-melanoma skin cancer in 4 (3.2%) and dysplastic nevus in 56 (44.4%). In the day of preplanned excision ATP was applied to the target lesion for 5–6 min and sent to the central lab. Amplifiable mRNA was found in all 126 ATP samples. 82 samples of 126 (65,1%) tested marker-positive. Sensitivity of RNA profiling for detection of skin cancers reached 88.14% (95% CI 77.07% – 95.09%), while specificity was only 53.85% (41.03% – 66.30%), with PPV of 63.41% (56.74% – 69.61%), NPV of 83.33% (70.65% – 91.22%) and accuracy of 70.16% (61.29% – 78.04%). Among the seven false negative results there were 3 M in situ and 4 invasive M. Conclusions: RNA profiling of skin ATP specimens is feasible and has high sensitivity but rather low specificity. Randomized studies are needed to evaluate if this technique can add anything to dermoscopy or other noninvasive diagnostic modalities. Clinical trial information: NCT04353050. [Table: see text]