ALK: Definition

by Jason Wasserman MD PhD FRCPC
April 6, 2026

ALK (anaplastic lymphoma kinase) is a gene that normally plays a role in the development of nerve cells. In healthy adult tissue, the ALK gene is essentially switched off, producing little to no protein. In some cancers, however, a structural change in the DNA causes the ALK gene to fuse with another gene — a process called a rearrangement. This fusion creates an abnormal, permanently active protein that drives cancer cell growth. Because the tumour depends on this abnormal protein to survive, drugs called ALK inhibitors can block it precisely — often producing strong and lasting responses. Testing for ALK is most commonly performed in lung cancer and certain lymphomas, where the result directly guides treatment decisions.

Why do pathologists test for ALK?

ALK testing is performed for two main purposes:

  • To determine eligibility for targeted therapy. ALK inhibitors — drugs such as alectinib, brigatinib, and lorlatinib — are specifically designed to block the abnormal ALK protein. They work only in tumors that carry an ALK rearrangement. Identifying this change is the prerequisite for using these treatments.
  • To help confirm the type of tumour. In some cancers, particularly anaplastic large cell lymphoma and inflammatory myofibroblastic tumour, the presence or absence of ALK is part of how the tumour is classified and influences prognosis and management.

Which cancers are commonly tested for ALK?

ALK testing is most important in:

  • Lung adenocarcinoma — approximately 3–7% of lung adenocarcinomas carry an ALK rearrangement. This is one of the most important biomarkers in lung cancer because ALK inhibitors are highly effective in this group, often outperforming standard chemotherapy. For full details, see the dedicated article on ALK rearrangements in lung cancer.
  • ALK-positive anaplastic large cell lymphoma (ALCL) — a type of lymphoma in which the ALK gene fuses with a gene called NPM1. ALK-positive ALCL generally has a better outlook than ALK-negative ALCL, and the ALK result is a key part of the diagnosis.
  • Inflammatory myofibroblastic tumour (IMT) — a soft tissue tumour in which ALK rearrangements are common and form part of the diagnostic criteria.

ALK changes are also found in a small number of other tumour types, including thyroid carcinoma, salivary gland carcinoma, and rare subtypes of kidney cancer. However, these are far less common contexts for ALK testing.

How is ALK tested?

Pathologists use several methods to test for ALK, often in combination:

  • Immunohistochemistry (IHC) — detects the ALK protein directly in tumour tissue. Because normal adult cells produce virtually no ALK protein, strong positive staining is a reliable indicator of an ALK rearrangement. IHC is fast and widely available, and a strongly positive result is often sufficient to start treatment.
  • FISH (fluorescence in situ hybridization) — looks directly at the DNA to detect a physical rearrangement of the ALK gene. FISH is used to confirm equivocal IHC results and, in some settings, as the primary test.
  • Next-generation sequencing (NGS) analyzes many genes simultaneously and can detect ALK rearrangements alongside other important biomarkers in a single test. This is the preferred approach at most major cancer centers.

How results are reported

ALK results are reported as either positive or negative:

  • ALK-positive (or ALK rearrangement detected) — an abnormal ALK change was found in the tumour. In lung cancer, this means ALK inhibitor therapy is appropriate. In ALCL, ALK positivity confirms the ALK-positive subtype and is associated with a better prognosis than in ALK-negative disease. In IMT, it supports the diagnosis.
  • ALK-negative (or ALK rearrangement not detected) — no abnormal ALK change was found. In lung cancer, this means ALK inhibitors are not expected to be effective, and other biomarkers will guide treatment. In lymphoma, it identifies the ALK-negative subtype, which has a different outlook and may require a different treatment approach.

Questions to ask your doctor

  • Was my tumour tested for ALK, and what was the result?
  • Does my ALK result make me eligible for ALK-targeted therapy?
  • What other biomarkers were tested alongside ALK, and what did they show?

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