How Gene Expression Profiling May Improve Melanoma Care
After a melanoma diagnosis, doctors use the cancer’s stage to help understand how serious it is and plan care. But staging cannot always predict whose melanoma will come back or spread.
A test called gene expression profiling (GEP) may offer another piece of information about that risk. It looks at the activity of certain genes in a tumor. Researchers are still studying how useful these results are when making care decisions.
In an interview with Dermatology Times, Gaurav Singh, MD, a Mohs surgeon at City of Hope Cancer Center in Chicago, discussed how he uses GEP testing for some people with melanoma of the skin. His comments describe his clinical approach, not a recommendation for everyone with melanoma. (Source: Dermatology Times interview)
Why melanoma staging does not tell the whole story
Doctors commonly use the American Joint Committee on Cancer (AJCC) staging system to describe melanoma. The stage takes into account factors such as how thick the tumor is, whether the skin over it has broken down, and whether cancer has reached nearby lymph nodes. Lymph nodes are small structures that help filter fluid and support the immune system.
These details are important, but they do not capture every factor that may affect how melanoma behaves. The tumor’s location, how quickly its cells are dividing, and whether a person’s immune system is weakened may also matter.
For example, some people with stage I melanoma have cancer that comes back or spreads even after standard treatment. Others with more advanced melanoma may do well after surgery and immunotherapy, which helps the immune system respond to cancer.
Singh described GEP testing as a possible way to identify tumors that may behave more aggressively than their stage alone suggests. The test is meant to add information to the usual assessment, not replace it. (Source: Dermatology Times interview)
How a gene expression test may be used
Singh discussed a test called DecisionDx-Melanoma, which looks at the activity of 31 genes in a melanoma tumor. He uses it to help assess risk in some people with stage I or stage II melanoma.
For someone with stage I melanoma, a result suggesting higher risk may lead to further discussion about imaging or a sentinel lymph node biopsy. This biopsy checks the first lymph node or nodes to which cancer is likely to spread. Singh said he may consider these options when the usual clinical features alone would not have led him to pursue them.
For stage II melanoma, he described using higher-risk results, including those labeled Class 2A or Class 2B, to inform decisions about additional imaging and closer follow-up. He may consider this even when a sentinel lymph node biopsy has not found cancer in the tested nodes. (Source: Dermatology Times interview)
Singh pointed to research using data from the Surveillance, Epidemiology, and End Results (SEER) program and findings from the prospective DECIDE study. These findings suggest that information about a tumor’s genes may help identify people who could be considered for closer monitoring. (Sources: SEER collaboration; DECIDE study)
That does not mean the test itself has been shown to improve survival. Its role in care is still being studied, and it should not replace established clinical assessments or guideline-based care.
Putting test results in perspective
A GEP result is only one part of the picture. Decisions about imaging, surgery, and follow-up also depend on a person’s overall health, ability to manage daily activities, other medical conditions, and preferences.
A lower-risk result may be reassuring, even if it does not change the care plan. A higher-risk result does not mean the melanoma will definitely come back or spread. It may instead prompt a discussion about whether closer observation would be useful.
Singh also noted that GEP testing may be less useful for some people with stage III melanoma when cancer has already been confirmed in the lymph nodes. Its value depends on the question the care team is trying to answer. (Source: Dermatology Times interview)
Could a blood test add more information?
Another area of research involves circulating tumor DNA, or ctDNA. These are small pieces of DNA from a tumor that may be found in the blood.
GEP testing and ctDNA testing provide different kinds of information. GEP looks at characteristics of the tumor that may be linked to future risk. CtDNA testing is being studied as a possible way to look for molecular signs of cancer over time.
Singh said he considers repeated ctDNA testing for some people whose GEP results suggest higher risk. In his practice, changes in those results may help inform later decisions about imaging. CtDNA testing in melanoma is still under investigation, and researchers are continuing to study how it might fit into follow-up care. (Source: Dermatology Times interview)
When to speak with a doctor
If you have melanoma or have had it treated, discuss any questions about testing, treatment, or follow-up with your doctor or dermatologist. They can help you understand what a test result may mean alongside your stage and personal circumstances.
Seek medical advice if you notice a new or changing mole or skin lesion, especially one that bleeds, is painful, or grows quickly. A doctor can assess the change and advise you on what to do next.
This article is for information only and is not a substitute for medical advice.
Sources
- Dermatology Times. Interview with Gaurav Singh, MD, about gene expression profiling in cutaneous melanoma.
- “31-gene expression profile testing in cutaneous melanoma and survival outcomes in a population-based analysis: A SEER collaboration.” JCO Precision Oncology, 7, e2300044. https://doi.org/10.1200/PO.23.00044
- “A prospective, multicenter analysis of recurrence-free survival after sentinel lymph node biopsy decisions influenced by the 31-GEP.” https://doi.org/10.1002/cam4.70839
- “The prognostic value of the 31-gene expression profile test in cutaneous melanoma: A systematic review and meta-analysis.” https://pubmed.ncbi.nlm.nih.gov/39518150/
- Bartlett, E. “Society of Surgical Oncology consensus statement: Assessing the evidence for and utility of gene expression profiling of primary cutaneous melanoma.” Annals of Surgical Oncology. https://doi.org/10.1245/s10434-024-16379-2
- “31-GEP (DecisionDx): A review of clinical utility and performance in a Mayo Clinic cohort.” https://pubmed.ncbi.nlm.nih.gov/39154363/