ALK (anaplastic lymphoma kinase)


ALK, short for Anaplastic Lymphoma Kinase, is a protein found inside certain cells in the body. It helps regulate how cells grow, divide, and survive. The ALK protein is normally active only in a few parts of the body, such as the brain and nervous system. However, changes in the ALK gene can cause it to become abnormally active in tumours, leading to uncontrolled cell growth and cancer. Because of this, pathologists test for ALK to help diagnose cancer and identify patients who may benefit from special treatments called ALK inhibitors.

What types of normal cells and tissues express ALK?

In healthy tissue, ALK expression is limited and is usually found only in small regions of the brain, nervous system, and testis. It is not normally present in most adult tissues. For this reason, when ALK is detected in a tumour, it usually signals an abnormal gene change.

How do pathologists test for ALK?

Pathologists test for ALK using a method called immunohistochemistry (IHC), which uses special antibodies to detect the ALK protein in a tissue sample. If ALK is present, it appears as a strong granular stain in the cytoplasm of tumour cells when viewed under a microscope. In some cases, ALK may also be seen on the cell membrane or in the nucleus, depending on the specific genetic alteration.

Other testing methods include:

A positive result suggests the tumour may respond to ALK-targeted therapy, while a negative result usually means the tumour does not have ALK-related changes.

What types of tumours express ALK?

ALK can be found in both benign and malignant (cancerous) tumours. Some of the more common ALK-positive tumours are listed below.

Lymphoid and soft tissue tumours:

  • Anaplastic large cell lymphoma (ALCL) – A type of non-Hodgkin lymphoma most commonly associated with ALK rearrangements.

  • Inflammatory myofibroblastic tumour (IMT) – A soft tissue tumour that may behave aggressively if ALK is present.

  • Epithelioid fibrous histiocytoma – A rare skin tumour that often shows ALK positivity.

  • Non-neural granular cell tumour – A rare tumour that expresses ALK in some cases.

Lung and solid organ tumours:

  • Lung adenocarcinoma – About 4% of lung adenocarcinomas have ALK rearrangements. These tumours are often sensitive to ALK inhibitors.

  • Thyroid carcinoma – Especially in the follicular variant of papillary thyroid cancer and poorly differentiated or anaplastic types.

  • Renal cell carcinoma (in children) – A rare form of kidney cancer that can show ALK positivity.

  • Salivary gland tumours – Certain rare types may express ALK, including secretory carcinoma and intraductal carcinoma.

Other ALK-positive tumours:

  • ALK-positive large B cell lymphoma – A rare subtype of aggressive lymphoma.

  • ALK-positive histiocytosis – A rare group of tumours involving immune system cells.

  • Spitz tumours – A type of melanocytic tumour that can show ALK fusions in some cases.

  • Colorectal and pancreatic cancer – ALK changes are very rare but may be found in a small number of cases.

Why is ALK important in a pathology report?

The presence of ALK is important because it may identify patients who can benefit from targeted treatments called ALK inhibitors, such as crizotinib, alectinib, or lorlatinib. These drugs block the activity of the abnormal ALK protein and can slow or stop tumour growth. ALK testing is especially important in lung cancer, where treatment decisions often depend on whether ALK rearrangements are present.

ALK results also help pathologists classify and subtype tumours. In some cancers, ALK positivity is part of the diagnostic criteria, meaning it helps confirm the type of tumour. ALK testing may also give information about prognosis, or how the tumour is likely to behave, and may be useful in clinical trial eligibility.

Questions to ask your doctor

  • What does the ALK result in my pathology report mean?

  • Does my tumour have an ALK gene rearrangement or mutation?

  • Am I eligible for ALK-targeted therapy?

  • Will additional genetic testing be needed?

  • How does ALK affect my diagnosis, treatment options, or prognosis?

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