ALK stands for anaplastic lymphoma kinase. It is a gene that provides instructions for making a protein involved in cell growth and communication. ALK is normally found in specific types of cells in the nervous system, where it helps regulate how these cells grow and function. However, changes in the ALK gene can occur, leading to abnormal activity that contributes to the development of cancer.
What is the normal function of ALK in a cell?
In normal cells, the ALK protein helps control the growth and development of nerve cells, particularly during early development. It acts as part of a signalling pathway, ensuring that cells grow and divide only when needed. Under normal conditions, ALK activity is tightly regulated, which helps maintain healthy tissues in the nervous system.
What types of cancer are associated with abnormal ALK?
Abnormal (mutated or rearranged) ALK is associated with several types of cancer. The most well-known is non-small cell lung cancer (NSCLC), particularly a subtype called ALK-positive adenocarcinoma, which accounts for a small percentage of lung cancer cases. In this subtype, a rearrangement of the ALK gene causes the production of an abnormal ALK protein that drives tumour growth.
Other cancers associated with abnormal ALK include:
- Anaplastic large cell lymphoma (ALCL): A type of non-Hodgkin lymphoma where abnormal ALK proteins are often found and play a significant role in the cancer’s development.
- Neuroblastoma: A cancer most commonly seen in children, where ALK mutations can contribute to tumour formation in nerve tissues.
- Inflammatory myofibroblastic tumour (IMT): A rare type of tumour that can arise in various body parts, often showing ALK rearrangements.
What kinds of tests do pathologists perform to look for abnormal ALK, and how will the tests be described in a pathology report?
Pathologists use several different tests to detect abnormalities in the ALK gene. The two most common tests are immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH).
- Immunohistochemistry (IHC): This test looks for abnormal ALK protein in tumour cells. If the IHC test shows strong staining, it suggests the tumour is ALK-positive.
- Fluorescence in situ hybridization (FISH): This test looks for specific rearrangements of the ALK gene in tumour cells. A positive FISH result indicates that the ALK gene has been altered, which can drive cancer growth.
If ALK testing is done, your pathology report will describe whether the tumour is ALK-positive or ALK-negative. A positive result means that the cancer cells show ALK abnormalities, which can influence treatment options. For example, ALK-positive cancers may respond to targeted therapies known as ALK inhibitors, which can block the activity of the abnormal ALK protein and slow or stop tumour growth.
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