FOLR1

FOLR1 is a gene that provides the instructions for making a protein called folate receptor alpha. This protein is found on the surface of specific cells and helps transport folate, a type of vitamin B (also known as vitamin B9), into the cell. Folate is essential because it enables cells to make DNA and RNA, which are the building blocks of cell growth and division.

In most normal adult tissues, FOLR1 is only found in very small amounts. However, in certain types of cancer, particularly those that grow rapidly, cells can produce significantly more of this protein. When this happens, the cancer cells can take in extra folate, which helps them grow faster.

Why is FOLR1 important in cancer?

FOLR1 is important in cancer because many tumors, especially epithelial tumors such as ovarian, breast, lung, and uterine cancers, produce higher than normal amounts of folate receptor alpha. This overproduction, or overexpression, makes FOLR1 a biomarker—a sign that doctors can use to help diagnose cancer and guide treatment.

In ovarian cancer, FOLR1 overexpression is especially common in high-grade serous carcinoma, one of the most aggressive forms of the disease. Research has shown that cancers with higher levels of FOLR1 may also exhibit more aggressive behavior, but they may respond better to specific targeted treatments.

How do pathologists test for FOLR1?

Pathologists test for FOLR1 using a laboratory technique called immunohistochemistry (IHC). This test utilizes specialized antibodies to detect the presence of folate receptor alpha on the surface of cancer cells. Only staining on the cell membrane (the cell’s outer wall) is considered when scoring the test, since this is where the receptor normally functions.

What do the test results mean?

For the test to be called positive, at least 75 percent of the cancer cells in the sample must show moderate (2+) or strong (3+) membrane staining. If this threshold is met, the cancer is considered FRα-positive, and the patient may be eligible for targeted therapy with targeted medications such as mirvetuximab soravtansine. If fewer cells are positive, the result is considered negative. In rare cases, results may be reported as indeterminate if there are too few cells or if the tissue sample is damaged.

What cancers are associated with FOLR1 overexpression?

FOLR1 overexpression is most often associated with:

• Ovarian cancer, particularly high-grade serous carcinoma, where up to 85 percent of cases may show increased FOLR1 levels.

• Endometrial cancer, especially specific aggressive subtypes.

• Lung cancer, particularly adenocarcinoma.

• Breast cancer, in a smaller percentage of cases.

• Uterine and ovarian carcinosarcomas, where recent studies also show high FOLR1 expression.

Why is FOLR1 testing important?

Testing for FOLR1 helps doctors:

• Guide treatment by identifying patients who may benefit from targeted therapy such as mirvetuximab soravtansine.

• Predict prognosis, as higher FOLR1 levels are sometimes associated with more aggressive disease.

• Support research, as new drugs targeting FOLR1 are being developed and tested in clinical trials.

Questions to ask your doctor

• Was my cancer tested for FOLR1 expression?

• What were the results of my FOLR1 test?

• Am I eligible for targeted therapy such as mirvetuximab soravtansine?

• How does FOLR1 testing affect my treatment plan?

• Should my tumor tissue be retested if my cancer comes back?