MITF (microphthalmia-associated transcription factor) is a protein that helps regulate the development, function, and survival of certain types of cells, particularly melanocytes. Melanocytes are specialized cells found in the skin and other tissues where they produce a pigment called melanin. This pigment gives color to the skin, hair, and eyes.
MITF plays a crucial role in cell function by controlling cell growth and pigment production genes. Changes in MITF function are associated with some types of cancer, particularly melanoma.
MITF is typically found in cells that produce melanin, specifically melanocytes, which are found in the skin, eyes, and other pigmented tissues. It can also be present in some immune cells.
Pathologists use immunohistochemistry (IHC) to detect MITF in tissue samples. In this test, antibodies bind specifically to the MITF protein if it is present in cells, resulting in a color change that can be observed under a microscope. This process allows pathologists to determine if MITF is present and assess the sample’s pattern and intensity of staining. The results are reported as either “positive” (MITF is present) or “negative” (MITF is absent), providing valuable information that can help identify specific types of cells or tumors, especially melanoma.
Most benign (noncancerous) tumours that express MITF are found in the skin and are made up of melanocytes.
Examples include:
MITF expression is seen in several malignant (cancerous) tumours, especially those derived from melanocytes.
Here are some cancers where MITF is commonly expressed:
Specific genetic changes in the MITF gene are associated with specific syndromes that affect pigmentation and sometimes increase cancer risk.
Syndromes associated with abnormal MITF include:
These syndromes illustrate how changes in MITF function can impact pigmentation and may increase the risk for certain health conditions, particularly melanoma. Genetic testing and counseling are often recommended for individuals with these syndromes to guide monitoring and management.
Pathologists and geneticists perform specialized genetic tests on DNA samples from blood or saliva to identify genetic syndromes linked to MITF. These tests analyze the MITF gene for specific mutations that can lead to health conditions like Waardenburg syndrome, Tietz syndrome, or familial melanoma syndrome. Key tests include:
Test: DNA sequencing of the MITF gene
Result: Heterozygous pathogenic variant detected in exon 8 of the MITF gene (c.952G>A; p.Gly318Arg)
Interpretation: A mutation was identified in the MITF gene associated with Waardenburg syndrome type 2. This variant, c.952G>A (p.Gly318Arg), is known to cause pigmentary abnormalities and hearing loss typical of the syndrome. This result confirms a diagnosis of Waardenburg syndrome type 2, and genetic counseling is recommended for the patient and family members.
In this example, a pathogenic variant in the MITF gene is reported. The result shows the specific mutation known to cause Waardenburg syndrome type 2, allowing for precise diagnosis and management planning.