A melanoma marker is a measurable substance or characteristic within the body that provides information about the cancer. These are distinct from the visual “ABCDEs”—Asymmetry, Border, Color, Diameter, and Evolving—which are clinical signs used for the initial identification of potentially cancerous moles. The markers discussed here are molecular in nature and are identified in a laboratory after a suspicious lesion has been surgically removed and biopsied. These biological indicators provide data that helps doctors confirm a diagnosis and select the most appropriate course of action.
The Role of Markers in Diagnosis and Staging
Once a skin lesion is biopsied, pathologists analyze the tissue to confirm if it is melanoma. This process often involves immunohistochemistry (IHC), a technique that uses antibodies to stain specific proteins on cells, highlighting them under a microscope. The presence of protein markers like S-100, Melan-A (also MART-1), and HMB-45 helps a pathologist distinguish melanoma from other types of skin cancer or benign moles. The specific pattern and intensity of the staining provide a high degree of diagnostic certainty.
Beyond confirming a diagnosis, markers also play a part in staging the disease. For individuals with stage IV melanoma, where the cancer has spread to distant parts of the body, a blood test for the enzyme Lactate Dehydrogenase (LDH) is used. Elevated levels of LDH in the bloodstream can indicate a larger tumor burden and a more aggressive disease course. This information is a factor for doctors in determining the patient’s prognosis and overall stage.
Genetic Markers and Targeted Therapy
A significant development in melanoma treatment has been the discovery of specific genetic mutations within tumor cells that drive their growth. These “driver mutations” are flaws in the cancer’s genetic code that create vulnerabilities for medications to exploit. This approach is the basis of targeted therapy, which aims to attack cancer cells directly while sparing most normal cells.
The most common driver mutation in melanoma occurs in the BRAF gene, with about half of all cutaneous melanomas having this mutation. This alteration causes the BRAF protein to be permanently active, leading to uncontrolled cell division. For patients whose tumors test positive for a BRAF mutation, a class of drugs called BRAF inhibitors can be used. These oral medications block the mutated protein, cutting off the signal that tells cancer cells to multiply.
To improve effectiveness and delay resistance, BRAF inhibitors are almost always given in combination with a MEK inhibitor, which blocks a different step in the same growth pathway. While BRAF is the most common target, other less frequent genetic markers also guide therapy. Mutations in genes such as NRAS and KIT are found in smaller subsets of melanoma patients, and their presence can still inform treatment decisions.
Markers for Immunotherapy
Another class of markers helps predict how a tumor will interact with the body’s immune system. This is central to immunotherapy, a treatment that empowers the patient’s own immune cells to fight the cancer. The focus here is on assessing the tumor’s defense mechanisms against an immune attack.
The immune system has natural “checkpoints” that prevent it from becoming overactive. One such checkpoint involves a protein called PD-1 on immune cells (T-cells) and its partner protein, PD-L1. Some cancer cells produce high levels of PD-L1 on their surface, which acts as a “brake” on the immune system when it connects with PD-1, allowing the cancer to hide.
The expression level of PD-L1 on tumor cells is a biomarker for immunotherapy. A higher level of PD-L1 expression can suggest that the cancer is relying on this cloaking mechanism to evade the immune system. This information helps doctors predict the effectiveness of checkpoint inhibitor drugs, which work by blocking the PD-1 and PD-L1 connection. This releases the “brake” on the T-cells, allowing them to recognize and attack the melanoma. A high PD-L1 level can indicate a greater likelihood of response, but patients with low or no PD-L1 expression can still benefit from immunotherapy.
How Melanoma Markers Are Tested
The journey to identifying melanoma markers begins with the tissue from a biopsy. In a pathology laboratory, technicians prepare the tissue and perform tests to look for the protein and genetic indicators that guide diagnosis and treatment.
For protein markers, the primary method is Immunohistochemistry (IHC). This technique applies antibodies to thin slices of tumor tissue, and a chemical stain makes the binding of these antibodies to specific proteins visible under a microscope. To find genetic markers for targeted therapy, laboratories use molecular sequencing techniques.
- Polymerase Chain Reaction (PCR) is a method that can rapidly copy a specific DNA segment, allowing for the detection of known mutations.
- Next-Generation Sequencing (NGS) can simultaneously read large sections of the tumor’s DNA to identify a wide range of mutations in multiple genes at once.
A more recent development is the liquid biopsy. This is a blood test that can detect circulating tumor DNA (ctDNA), which are fragments of DNA shed by cancer cells into the bloodstream. While not a replacement for the initial tissue biopsy, liquid biopsies are increasingly used to monitor a patient’s response to treatment or to check for new mutations, offering a less invasive way to track the cancer’s evolution.