Gene‑expression test predicts negative sentinel nodes—could it spare patients an invasive biopsy?

Education and decision-support only — not a medical device or personalised advice. Always discuss your specific situation with your specialist team.

Context

The 2025 MERLIN_001 study found that a melanoma gene‑expression profile (GEP) test correctly identified 94 % of patients with cancer‑free sentinel nodes, giving a high negative‑predictive value ¹. This suggests the test could eventually spare many patients an invasive sentinel lymph node biopsy (SLNB).

Introduction

People diagnosed with early‑stage melanoma often wonder whether a sentinel lymph node biopsy is necessary. The decision hinges on the likelihood that cancer has already spread to the first draining lymph node. SLNB is the standard method for detecting microscopic spread, but the procedure can cause pain, infection, and swelling. A new GEP test measures the activity of dozens of melanoma‑related genes in the primary tumor and predicts that risk. After reading this article you will understand what the test measures, recognize its strengths and gaps, and know which questions to raise with your dermatologist or oncologist.

Can the gene‑expression test reliably rule out sentinel node involvement?

The MERLIN_001 trial evaluated a GEP assay that quantifies expression of 31 melanoma‑related genes in the primary tumor and feeds the result into a predictive algorithm ¹. In the 188‑patient cohort, the test yielded a negative‑predictive value of 94 %, meaning that when the test said “low risk,” 94 % of those patients truly had a negative sentinel node ¹. Sensitivity was lower, at 68 %, reflecting that some node‑positive cases were missed by the assay ¹. The authors argued that the high negative‑predictive value could justify omitting SLNB in selected low‑risk patients, but they cautioned that the residual false‑negative rate (about 6 %) must be weighed against the morbidity of surgery ¹.

What are the known limitations of the MERLIN_001 findings?

The study enrolled fewer than 200 patients, limiting statistical power to detect rare false‑negative events and to explore sub‑group performance such as thick versus thin melanomas ¹. Because it was conducted at a single academic center, the patient population was relatively homogeneous, raising questions about how the test will perform in broader, more diverse clinical settings ¹. A small subset of patients with a “low‑risk” GEP result still harbored microscopic nodal metastases, indicating a residual false‑negative risk that cannot be ignored ¹. The assay was not directly compared with existing clinical nomograms that combine tumor thickness, ulceration, and patient age, so its incremental value over standard risk calculators remains unclear ¹.

How might the test change patient pathways if validated?

If larger, multi‑center trials confirm the MERLIN_001 performance, clinicians could use the GEP test early after melanoma excision to stratify patients into low‑ and high‑risk groups for nodal spread ¹. Low‑risk patients might forego SLNB and instead follow a surveillance schedule of regular skin exams and periodic imaging, reducing exposure to surgical complications such as lymphedema or wound infection ¹. High‑risk patients would still be directed to SLNB, potentially accelerating detection of nodal disease and timely adjuvant therapy. Adoption would require updates to national melanoma guidelines, insurance reimbursement policies, and clear communication of the test’s false‑negative rate to patients ¹. Until such evidence accumulates, the test remains investigational and should be offered only within a clinical trial or after thorough discussion with a specialist ¹.

What This Means for You

The current data suggest the GEP test can identify many melanoma patients whose sentinel nodes are likely cancer‑free, but the evidence is still limited to a single, modestly sized study ¹. Because a small percentage of low‑risk results still hide nodal disease, the test cannot yet replace the standard SLNB in routine practice. Discuss the availability, accuracy, and cost of the test with a qualified dermatologist, and consider it only in the context of a clinical trial or when standard risk models leave you uncertain. Keep any test results handy and share them with all members of your care team to ensure decisions are made with the full picture. Always discuss any changes to your care or screening plan with a qualified dermatologist.

TL;DR

• If the test says low risk, it is correct about 94 % of the time. ¹
• The assay reads activity of 31 melanoma‑related genes to estimate sentinel node involvement.
• Evidence comes from a single‑center cohort of < 200 patients; false‑negatives still occur. ¹
• Ask your dermatologist to explain the result and whether the test fits your case or a trial.
• Larger multi‑center trials are needed before the test can guide routine care.

Additional references

[2] Zager JS, Gastman BR, Leachman S, et al. The 31-gene expression profile test informs sentinel lymph node biopsy decisions in patients with cutaneous melanoma: results of a prospective, multicenter study. Curr Med Res Opin. 2023;39(2):213–219. PMID 36617959

[3] Integrating the melanoma 31-gene expression profile test with clinical and pathologic features can provide personalized precision estimates for sentinel lymph node positivity: an independent performance cohort. World J Surg Oncol. 2024. PMID 39215342