The LDH Test for Melanoma and Detection of Metastasis

LDH is a blood test that measures the amount of lactate dehydrogenase (LDH), an enzyme, in your blood.1 Chemically, LDH works to convert pyruvate to lactate in your body.2 You may be familiar with lactate, as it is what accumulates in your body after a heavy workout and makes you feel sore.

Overview

In general, LDH is measured to check for tissue damage in areas such as your heart, liver, kidney, skeletal muscle, brain, and lungs — all of which, if injured, elevate the level of LDH in your blood.3 If you have advanced melanoma, your healthcare provider can use this test to help determine if your cancer has metastasized or spread to organs beyond your skin and lymph nodes. LDH is not commonly ordered for early melanoma. Healthcare providers have found it most reliable in patients with metastatic disease.4

Your healthcare provider may check your LDH levels as part of the initial staging of melanoma, particularly if you have advanced disease. LDH levels have implications for prognosis and can be used to monitor response to therapy and to monitor for recurrence of disease.

The most common areas for cancer to progress are usually the liver or lungs.5 Although LDH is not specific to melanoma, it can be a useful test for diagnosing or monitoring skin cancer post-surgical treatment.6 The staging system for melanoma also uses the results of any LDH testing to subdivide patients with stage IV disease.

How the Test Is Performed

To determine your LDH levels, your healthcare provider will draw blood from your vein or from your heel, finger, toe, or earlobe.7 The laboratory then quickly spins the blood to separate the serum, the liquid portion of your blood, from the blood cells. The LDH test is performed on your blood serum.

Before you have blood drawn, your healthcare provider may ask you to stop taking certain drugs known to affect LDH. Drugs that can increase LDH include alcohol, anesthetics, aspirin, clofibrate, fluorides, mithramycin, narcotics, and procainamide.8

What Test Results Mean

Normal values may vary depending on your age, sex, and the specific method used in the laboratory. The normal reference range is typically 105 to 333 IU/L (international units per liter).9 The total LDH is often further separated into five components (called isoenzymes) — LDH-1, LDH-2, LDH-3, LDH-4, and LDH-5 — that are specific to certain regions of the body and are expressed as percentages of the total.10

LDH level can be elevated in many conditions, not just metastatic melanoma. Higher-than-normal levels may also indicate:11

• Stroke
• Heart attack
• Various kinds of anemia
• Low blood pressure
• Liver disease (for example, hepatitis)
• Muscle injury
• Muscular dystrophy
• Pancreatitis

Falsely elevated results can happen if the blood specimen was handled roughly, stored in extreme temperatures, or if the sample was difficult to collect.12

What Research Shows

Prior studies have shown that an elevated LDH level can predict survival in patients with advanced melanoma.13 For this reason, LDH was included in the 2002 staging system for melanoma.14 Patients with stage IV melanoma and elevated LDH have the worst prognosis.

Beyond categorizing patients with stage IV disease, the LDH test is not specific or sensitive enough to detect melanoma before it metastasizes to the lymph nodes.15 A study followed patients with melanoma for 2.5 years after surgery. The results showed that LDH level was not a good marker for "in-transit metastasis" (stage IIIC melanoma that has spread beyond the skin lesion but not to the lymph nodes) or spread to local lymph nodes. In the study, the LDH test only accurately identified distant metastasis in a minority of patients.16 A test for another blood protein called S-100B is emerging as a better marker than LDH and may be incorporated into future staging systems.17

If your healthcare provider has ordered a test for LDH, or even if the results come back and the level is high, do not panic. A high LDH level does not mean your melanoma has metastasized, it is only a "head's up" for your healthcare provider to investigate the situation further with a CT, PET, or MRI scan or sentinel lymph node biopsy. If you have any questions or concerns about interpreting your LDH test results, be sure to discuss them with your healthcare provider.