FLI1


FLI1 (Friend leukemia integration 1) is a protein produced by a gene located on chromosome 11. It belongs to a family of proteins known as ETS transcription factors, which play an important role in controlling cell growth, differentiation, and development. Pathologists often test for FLI1 to help diagnose certain types of cancers, especially Ewing sarcoma and vascular tumors.

What types of normal cells and tissues express FLI1?

In normal, healthy tissues, FLI1 is commonly found in:

  • Endothelial cells, which line blood vessels

  • T and B lymphocytes, which are important components of the immune system

How do pathologists test for FLI1?

Pathologists perform a test called immunohistochemistry (IHC) to identify FLI1 in tissue samples. This test involves applying a special antibody that attaches to the FLI1 protein within the cell nuclei (the central part of cells containing genetic material). When FLI1 is present, the nuclei stain clearly under the microscope. A result is considered positive if at least 10% of tumor cells show nuclear staining, though it is usually higher (often over 50%).

In addition to immunohistochemistry, pathologists may perform molecular tests such as next-generation sequencing (NGS) or fluorescence in situ hybridization (FISH) to look specifically for genetic changes involving the FLI1 gene. For example, Ewing sarcoma commonly contains a gene fusion called EWS-FLI1, which results from the combination of the EWS gene on chromosome 22 and the FLI1 gene on chromosome 11. Detecting this fusion by molecular testing helps confirm the diagnosis of Ewing sarcoma, particularly in cases that are difficult to distinguish from other tumor types based on microscopic appearance alone.

What types of tumors express FLI1?

FLI1 is expressed in several types of tumors, including:

  • Ewing sarcoma / Primitive neuroectodermal tumor (PNET): About 90% of these tumors express FLI1, making this marker useful to differentiate Ewing sarcoma from other similar-looking tumors.

  • Vascular tumors: Around 94% of both benign and malignant vascular tumors (such as angiosarcomas and hemangioendotheliomas) express FLI1.

  • Astrocytomas (brain tumors): Moderate to strong staining is common (81%), particularly in higher-grade tumors (grade III and IV).

  • Lymphoblastic lymphoma: About 85% of these tumors express FLI1, with variable expression in other types of lymphoma.

  • Melanoma: Approximately 50% express FLI1, but only a small percentage (4%) show strong staining.

  • Merkel cell carcinoma: Frequently positive (90%).

  • Epithelioid sarcoma: High frequency of expression (93%).

  • Mesothelioma: Almost always positive (95%).

What types of tumors do not express FLI1?

Tumors typically negative for FLI1 include:

  • Desmoplastic small round cell tumor

  • Blastema predominant Wilms tumor

  • Small cell osteosarcoma

  • Germ cell tumors

  • Tumors derived from muscle, nerve, and fibroblast cells

This distinction is important to pathologists when making an accurate diagnosis, as some of these negative tumors can look similar to Ewing sarcoma under the microscope.

How do pathologists interpret FLI1 results?

Pathologists interpret FLI1 results based on the presence of nuclear staining in tumor cells:

  • Positive result: At least 10% of tumor cells show nuclear staining (often >50%). This suggests a diagnosis such as Ewing sarcoma or a vascular tumor.

  • Negative result: Less than 10% of tumor cells show staining, or no staining is seen. This helps rule out certain cancers and directs pathologists to other diagnoses.

Because FLI1 can be expressed in multiple tumor types, additional tests (such as molecular testing for specific genetic changes like the EWS-FLI1 fusion gene) are often required to confirm the diagnosis.

Prognostic significance of FLI1

FLI1 expression levels can have prognostic significance in some cancers:

  • Astrocytomas: High FLI1 expression is associated with a worse prognosis.

  • Nonsmall cell lung carcinoma: Increased FLI1 expression is linked to a poorer outcome.

  • Endometrial cancer: Overexpression of FLI1 predicts an adverse prognosis.

These findings suggest that measuring FLI1 expression may help predict how aggressive certain cancers may be.

Questions for your doctor

  • Was my tumor tested for FLI1, and what was the result?

  • How does my FLI1 test result influence my diagnosis?

  • Does a positive FLI1 result affect my treatment options?

  • Are there additional tests needed to confirm my diagnosis?

  • Does the presence or absence of FLI1 impact my prognosis or the likelihood of cancer spreading or recurring?

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