Gene expression profiling (GEP) has been integrated into cancer treatment decision‐making in multiple neoplasms.,We prospectively evaluated the prognostic utility of the 31‐GEP test (DecisionDx‐Melanoma, Castle Biosciences, Inc) in cutaneous melanoma (CM) patients undergoing sentinel node biopsy (SNB).,One hundred fifty‐nine patients (age 26‐88) diagnosed with melanoma between 01/2013 and 8/2015 underwent SNB and concurrent GEP testing.,GEP results were reported as low‐risk Class 1 (subclasses 1A and 1B) or high‐risk Class 2 (subclasses 2A and 2B).,Statistical analyses were performed with chi‐square analysis, t tests, log‐rank tests, and Cox proportional hazard models.,Recurrence‐free survival (RFS) and distant metastasis‐free survival (DMFS) were estimated using Kaplan‐Meier method.,Median follow‐up was 44.9 months for event‐free cases.,Median Breslow thickness was 1.4 mm (0.2‐15.0 mm).,There were 117 Class 1 and 42 Class 2 patients.,Gender, age, Breslow thickness, ulceration, SNB positivity, and AJCC stage were significantly associated with GEP classification (P < 0.05 for all).,Recurrence and distant metastasis rates were 5% and 1% for Class 1 patients compared with 55% and 36% for Class 2 patients.,Sensitivities of Class 2 and SNB for recurrence were 79% and 34%, respectively.,Of 10 SNB‐positive/Class 2 patients, 9 recurred.,By multivariate analysis, only SNB result and GEP class were statistically associated with both RFS (P = 0.008 and 0.0001) and DMFS (P = 0.019 and 0.001).,Gene expression profiling Class 2 result and SNB positivity were independently associated with recurrence and distant metastasis in primary CM patients.,GEP testing may have additive prognostic utility in initial staging work‐up of these patients.
Clinical and histopathologic assessment of pigmented skin lesions remains challenging even for experts.,Differentiated and accurate noninvasive diagnostic modalities are highly desirable.,We sought to provide clinicians with such a tool.,A 2-gene classification method based on LINC00518 and preferentially expressed antigen in melanoma (PRAME) gene expression was evaluated and validated in 555 pigmented lesions (157 training and 398 validation samples) obtained noninvasively via adhesive patch biopsy.,Results were compared with standard histopathologic assessment in lesions with a consensus diagnosis among 3 experienced dermatopathologists.,In 398 validation samples (87 melanomas and 311 nonmelanomas), LINC00518 and/or PRAME detection appropriately differentiated melanoma from nonmelanoma samples with a sensitivity of 91% and a specificity of 69%.,We established LINC00518 and PRAME in both adhesive patch melanoma samples and underlying formalin fixed paraffin embedded (FFPE) samples of surgically excised primary melanomas and in melanoma lymph node metastases.,This technology cannot be used on mucous membranes, palms of hands, and soles of feet.,This noninvasive 2-gene pigmented lesion assay classifies pigmented lesions into melanoma and nonmelanoma groups and may serve as a tool to help with diagnostic challenges that may be inherently linked to the visual image and pattern recognition approach.