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- Presentation
Gene Expression Profiling in Melanoma: Current Utility, Commercial Assays, and Guideline Limitations
Description
The talk reviewed gene expression profiling (GEP) in melanoma, explaining that these assays measure differential gene activity from biopsy or excision tissue to estimate tumor biology and risk. GEP is appealing because standard clinicopathologic staging and nomograms can miss biologic heterogeneity, potentially leading to over- or underestimation of sentinel lymph node (SLN) risk, recurrence risk, and treatment decisions. The speaker reviewed traditional risk calculators from MSKCC and the Melanoma Institute of Australia, noting that although they help with shared decision-making, their performance is limited in early T1 disease and low-risk ranges. Commercial assays were then discussed: diagnostic tests such as DermTech’s tape test, MyPath/DIF-DX, and prognostic tests including DecisionDx (31-GEP), Merlin CPGEP/8-GEP, and Melogenics. While many report promising sensitivity or prognostic associations, real-world validation has been inconsistent, with concerns about false positives, false negatives, overlapping cohorts, short follow-up, and industry bias. Current guidelines remain cautious: NCCN largely advises that predictive GEP tests should not replace SLN biopsy decisions, though a narrow use case for CPGEP in select T1B/T2A patients has been added; AAD and European guidelines do not recommend GEP as a standalone tool, and surgical oncology groups consider these assays investigational. The speaker concluded that GEP may eventually improve individualized risk prediction, surveillance, and therapy selection, but stronger prospective, unbiased evidence is still needed before routine broad adoption.
View moreConclusions
- Gene expression profiling in melanoma is promising for capturing tumor biology beyond traditional staging, but it still cannot reliably replace clinicopathologic assessment or sentinel lymph node biopsy.
- Current nomogram-based risk tools and many commercial GEP assays show only moderate or inconsistent performance, especially in early T1 disease and in low-risk probability ranges.
- Among prognostic assays, the evidence suggests the strongest current clinical niche is limited to select T1B to T2A patients when deciding whether sentinel lymph node biopsy might reasonably be deferred.
- The 31-GEP/DecisionDx-Melanoma assay can stratify recurrence risk, but its real-world sensitivity, specificity, and false-negative/false-positive rates remain concerning and have not yet proven improved survival outcomes.
- The Merlin CP-GEP assay appears promising in prospective validation, with high assay success and high negative predictive value in selected patients, but it still produces meaningful false negatives and has not yet shown outcome superiority over simpler tools.
- The MelanoGx/MelaGenix assay and other newer prognostic tests remain investigational until longer-term prospective data demonstrate that they improve management and patient outcomes.
- Diagnostic GEP assays for challenging melanocytic lesions may help in selected difficult cases, but available evidence is variable and they should not be used as standalone replacements for expert pathology and ancillary testing.
- Across society guidelines, GEP testing in cutaneous melanoma is still viewed cautiously, with most organizations recommending that it not replace sentinel node staging or drive adjuvant treatment decisions on its own.
- The ideal melanoma GEP test would provide continuous, clinically meaningful risk prediction that improves biopsy selection, surveillance planning, and treatment decisions, but no current assay fully meets that standard.
- Future progress in melanoma GEP will depend on independent prospective validation, better calibration for specific subgroups, longer follow-up, and clearer demonstration of benefit in real-world patient outcomes.
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- Olofsson Bagge et al. JAMA Surgery, 2024. (MSKCC SLN Risk Nomogram citation as referenced on slide)
- Marchetti MA, Coit DG, Dusza SW, et al. Performance of Gene Expression Profile Tests for Prognosis in Patients With Localized Cutaneous Melanoma: A Systematic Review and Meta-analysis. JAMA Dermatol. 2020;156(9):953-962. doi:10.1001/jamadermatol.2020.1731.#10.1001/jamadermatol.2020.1731
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- NeraCare / MelaGenix. European Journal of Cancer, 2021. PMID:33278769.