The Integrated 31-Gene Expression Profile Test (i31-GEP) for Cutaneous Melanoma Outperforms the CP-GEP at Identifying Patients who can Forego Sentinel Lymph Node Biopsy when Applying NCCN Guidelines

Main Article Content

Alex Glazer
Michael Tassavor
Dustin Portela
Teo Soleymani


genomics, sentinel, lymph node biopsy, melanoma, GEP, clinicopathologic


Introduction: Eighty-eight percent of patients who receive a sentinel lymph node biopsy (SLNB) receive a negative result. Current guidelines suggest avoiding SLNB if the risk of positivity is <5%. A low threshold for performing SLNB indicates worry about missing positive nodes but results in many unnecessary biopsies. The integrated 31-gene expression profile (i31-GEP) test combines the 31-GEP with Breslow thickness, age, ulceration, and mitotic rate using a validated neural network algorithm to identify patients with <5% risk by reporting a precise, individualized likelihood score. Using logistic regression, a separate GEP (8 genes plus Breslow thickness and age; CP-GEP) also aims to identify patients who can forego SLNB by binning patients into low- and high-risk categories. This study compared the i31-GEP for SLNB with the CP-GEP to identify patients who can safely forego SLNB.

Methods: This study evaluated the genes, gene pathways, and relative contribution of the two gene signatures relative to clinical and pathologic factors and further analyzed patients with T1b-T2 tumors from previously published studies in U.S. cohorts for the i31-GEP (n=763) and CP-GEP (n=153). A ratio of true-to-false-negative i31-GEP for SLNB and CP-GEP test results was compared to the guideline-established ratio of 19 negatives to one missed positive (19:1) if foregoing SLNB using a 5% risk threshold.

Results: The i31-GEP had a 30:1 true-to-false-negative ratio, compared to 15:1 using CP-GEP. In T1b tumors, the i31-GEP ratio increased to 35:1 compared to 14:1 using CP-GEP.

Limitations: Retrospective design, which could lead to bias. Patients included in both analyses were primarily from institutional surgical centers, and referral bias may not make the result generalizable.

Conclusion: Only the i31-GEP provided benefit over guideline-established care for identifying patients with low risk of SLN positivity.


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