PRAME

PRAME stands for “preferentially expressed antigen in melanoma.” It is a special type of protein called a cancer-testis antigen. This means that PRAME is usually found in cancer cells and normal cells within the testis, but rarely in other normal tissues of the body. Because PRAME is mostly found in cancer cells, pathologists often test for this protein to help diagnose certain types of cancers, especially melanoma, a type of skin cancer.

What types of normal cells and tissues express PRAME?

In normal, healthy tissues, PRAME is primarily expressed in the testis, particularly in cells involved in the early stages of sperm production. It is also found at lower levels in some other tissues, such as the ovaries, placenta, adrenal glands, and endometrium. PRAME expression in these tissues is normal and not associated with disease.

How do pathologists test for PRAME?

Pathologists test for PRAME using a special laboratory technique called immunohistochemistry. This test involves applying antibodies that specifically attach to PRAME proteins in tissue samples. When PRAME is present, the antibodies bind to it, resulting in visible nuclear staining under the microscope. Pathologists evaluate whether the staining is diffuse (seen in most cells) or focal (limited to a few cells). Typically, diffuse staining is associated with cancers like melanoma, while benign (non-cancerous) conditions usually show little or no staining.

What types of benign (non-cancerous) tumors express PRAME?

Most benign tumors, such as common skin moles (nevi), are usually negative or show only focal or patchy staining for PRAME. Diffuse or widespread staining in benign tumors is very rare. For instance, while a small percentage (around 13–19%) of nevi can show focal PRAME staining, very few demonstrate diffuse positivity. Similarly, benign nerve sheath tumors rarely express PRAME, and if they do, the expression is weak and limited to very few cells.

What types of malignant (cancerous) tumors express PRAME?

PRAME is frequently found in melanoma, including primary skin melanomas, metastatic melanomas (melanomas that have spread), and melanomas affecting mucosal surfaces. Approximately 70–95% of primary melanomas (non-spindle type) and around 90% of metastatic melanomas show diffuse PRAME staining. PRAME is also expressed by other types of cancers, including certain sarcomas (like synovial sarcoma and myxoid liposarcoma), malignant peripheral nerve sheath tumors, some leukemias and lymphomas, and certain carcinomas such as ovarian, endometrial, lung, breast, salivary gland, and germ cell tumors.

Why do pathologists test for PRAME?

Pathologists test for PRAME to help distinguish between melanoma and benign skin lesions like moles. Diffuse PRAME staining strongly supports a diagnosis of melanoma, while negative or focal staining favors a benign lesion. PRAME testing can also assist pathologists in:

• Determining if melanoma has spread to lymph nodes.

• Accurately assessing tumor margins, especially for melanoma in situ.

• Clarifying difficult-to-interpret cases where melanoma and benign conditions appear similar under the microscope.

• Providing information about the risk of melanoma spreading, particularly for eye melanomas (uveal melanomas), as part of specific prognostic tests.

Questions for your doctor

• Was PRAME tested on my biopsy or surgery specimen, and what were the results?

• Does the presence or absence of PRAME affect my diagnosis or treatment plan?

• Is additional testing needed based on my PRAME results?

• If PRAME was positive, does this indicate my cancer is more aggressive or likely to spread?

• How will the PRAME results influence my follow-up care?

• Are there other tests you recommend based on the PRAME findings?