FOXL2 is a gene and the protein it makes. The FOXL2 protein helps the ovary develop and keeps ovarian cells working normally. Pathologists test for FOXL2 in two ways. A protein test helps identify sex cord-stromal tumors of the ovary. A gene test looks for one specific change that almost every adult granulosa cell tumor carries.
This article explains the FOXL2 protein stain, the FOXL2 C134W mutation test, and what each FOXL2 result on your report means.
FOXL2 is a transcription factor, a protein that switches other genes on and off. It works inside the nucleus of the cell. FOXL2 is active in the supporting cells of the ovary, called granulosa cells. It is also active in some other cells around the eggs and in the ovarian stroma.
FOXL2 helps the ovary develop before birth and keeps it functioning through adulthood.
Pathologists test for the FOXL2 protein using immunohistochemistry. This test uses an antibody that sticks to FOXL2 in a thin slice of tissue. Cells that contain FOXL2 show brown staining in their nuclei under the microscope.
FOXL2 protein is a marker for sex cord-stromal tumors of the ovary. These tumors start in the ovary’s supporting and hormone-making cells. In one large study, more than 95 percent of these tumor types were positive:
About half of Sertoli-Leydig cell tumors were also positive. Almost all tumors outside this group were negative. This makes a positive result strong evidence for a sex cord-stromal tumor.
FOXL2 is a sensitive and specific marker, but no single marker catches every case. About 1 in 5 sex cord-stromal tumors in that study were FOXL2-negative. Most of these were Sertoli-Leydig cell tumors.
For this reason, pathologists usually test FOXL2 together with other markers. The panel often includes inhibin, calretinin, and SF-1. At least one of FOXL2, inhibin, or calretinin was positive in almost every sex cord-stromal tumor.
The FOXL2 C134W mutation is a small change in the FOXL2 gene. It changes one building block of the FOXL2 protein. This change occurs only in the tumor cells, not in the rest of the body. It is not inherited and does not pass to children.
The mutation is closely tied to adult granulosa cell tumor:
A FOXL2 mutation test helps confirm a diagnosis of adult granulosa cell tumor. This tumor can look like other ovarian tumors under the microscope. Finding the C134W mutation strongly supports the diagnosis.
The test is especially helpful in difficult cases. Examples include a tumor with unusual features or a tumor that returns years after surgery. The test is a type of molecular testing. It checks the tumor’s DNA rather than its proteins.
Your report may include a FOXL2 protein result, a FOXL2 mutation result, or both: