Dermatologists understand the concern and danger patients face when biopsies reveal melanoma. Since almost 7,000 Americans are predicted to die from melanoma in 2020, and some therapeutic regimens for advanced disease are contingent upon molecular tumor markers, clinics must take an active role in accelerating the molecular testing process.

Dermatologists can benefit from a baseline understanding of molecular testing. By identifying why molecular tests are ordered, exploring the most common forms of testing, and examining the testing workflow, dermatologists can help to ensure their patients receive life-saving care.

Why are molecular tests ordered?

When a diagnosis of advanced melanoma occurs, molecular diagnostic testing is critical to revealing opportunities for targeted therapies and immunotherapies. Targeted therapies treat melanoma by inhibiting genetic driver mutations. One of the most commonly mutated genes in melanoma is BRAF, which affects about 50 percent of all melanoma cases. Mutations in the BRAF gene produce a protein that can cause cancerous cells to grow and divide. In addition, tumors with certain BRAF mutations are sensitive to targeted therapy with BRAF and MEK inhibitors, which is associated with prolonged survival. Another commonly mutated gene in melanoma is NRAS, which can also be targeted by MEK inhibitors.

Melanomas with mutations in the C-KIT gene are less common but can also be tested for. Typically, C-KIT melanomas occur on the palms, hands, feet, or mucosal areas like the mouth. Some targeted therapies, such as imatinib, can be utilized in tumors with C-KIT mutations.

Immunotherapy utilizes the body’s own immune system to treat melanoma tumors. A biomarker called tumor mutational burden has been associated with response to immunotherapies. Tumor mutational burden can be determined by certain types of molecular testing.

Molecular testing is recommended for at-risk patients with stage 3 and stage 4 metastatic melanoma. While stage 3 can suggest satellite tumors or multiple lymph nodes matted together, stage 4 indicates cancer has spread to other areas of the body, such as the liver, soft tissue, spinal cord, or lungs. A patient in either stage can expect surgery, targeted therapy and/or immunotherapy, and possible radiation treatment.

What are the most common forms of testing?

When testing detects cutaneous malignant melanoma in the early localized stage, patients have a five-year survival rate of 99 percent. However, a belated diagnosis that results in cancer spreading to regional or distant locations can reduce the five-year survival rate to as little as 25 percent.

Molecular testing is most commonly performed on a sample of the patient’s melanoma tumor. Testing procedures are often determined by what is covered by the patient’s insurance. Next-Generation Sequencing (NGS) performs full characterization and provides the most genetic information. This highly sensitive test can identify mutations in melanoma tumor tissue simultaneously in BRAF and hundreds of other genes, including NRAS and C-KIT. Some NGS tests can also measure tumor mutational burden, a biomarker for response to immunotherapy.

Real-time polymerase chain reaction (RT-PCR) is another form of molecular testing that detects the most common mutations (hot spot mutations) in a gene. While PCR testing specializes in low numbers of gene targets, it can offer faster turnaround time for results when only one or a few genes are of interest. NGS testing can simultaneously detect mutations across thousands of target regions. Either of these genetic tests is optimal for BRAF mutation analysis.

What is the molecular testing workflow?

Traditionally, oncologists handle molecular testing. However, dermatologists can speed up the process by requesting the tests from their dermatopathology lab partner, which should have protocols to manage and report mutation tests. Experienced full-service dermatopathology labs like PathologyWatch stay up to date on the latest molecular testing processes. In addition to managing tests for dermatology clinics, the academic-level dermatopathologists at PathologyWatch also manage testing for oncologists.

Once the laboratory makes the melanoma diagnosis, EMR integration is a reliable way to share fast and accurate results with the dermatologist, who is an integral part of the patient’s care team. After receiving the results, the dermatologist can refer the patient to an oncologist, who will start life-saving treatment based on the molecular testing results.

Though representing only 1 percent of all skin cancers, melanoma’s ability to spread to other parts of the body makes it highly lethal. As a dermatologist, knowing why molecular tests are ordered, understanding the different types of testing, and being aware of the testing workflow can help you get your patients the prompt treatment they require.