Summary

This test detects specific ALK gene rearrangements – a form of mutation – in tumour tissue in order to guide non-small cell lung cancer (NSCLC) therapy. The presence of an ALK gene rearrangement makes it more likely that a person with non-small cell lung cancer (NSCLC) will respond to drug therapy specifically targeted at the ALK kinase. 
 

Why get tested?

An ALK mutation test is usually requested if you have been diagnosed with non-small cell lung cancer (NSCLC) especially adenocarcinoma and your doctor may consider a therapeutic management plan that includes an ALK kinase inhibitor such as crizotinib. Non-small cell lung cancer also includes squamous cell carcinoma, large cell carcinoma as well as some rarer types of lung cancer.

It is typically requested along with or as a follow-up test to EGFR mutation testing. If a non-small cell lung cancer has an EGFR mutation, then you are likely to respond to an anti-EGFR drug therapy (tyrosine kinase inhibitor) and further testing is usually not necessary.

However, if the tumour is negative for an EGFR mutation, then you are not likely to respond to an anti-EGFR tyrosine kinase inhibitor. ALK mutation testing is then used to determine whether your tumour would be likely to respond to an ALK kinase inhibitor.

What is an ALK gene rearrangement?
ALK is a short name for the anaplastic lymphoma receptor tyrosine kinase gene.  About 5 per cent of people who have NSCLC, in particular adenocarcinoma, have an inversion on the short arm of chromosome 2 which leads to the fusion of the ALK gene with another gene called EML4.

This reversing of a piece of DNA results in the production of an EML4-ALK fusion protein. Less commonly, fusion of the ALK gene with other genes such as TFG or KIF5B can occur.

The abnormal production of the altered ALK protein promotes the uncontrolled growth of cancer cells but it also makes it more likely that if you have this you will respond to a drug that targets the abnormal protein – an ALK kinase inhibitor, such as crizotinib –and less likely that you will respond to tyrosine kinase inhibitors that target the epidermal growth factor receptor (EGFR) (See EGFR Mutation Testing).

The test
The test is available in some larger laboratories, but most often it will be sent to a specialised reference laboratory. The two main methods of ALK testing are:

Fluorescent in situ hybridization (FISH)—this method looks for the presence of an ALK gene rearrangement at the chromosomal level. It is currently the gold standard for detection of ALK gene rearrangements in NSCL.

Immunohistochemistry (IHC)—this method uses antibodies to detect the presence of an altered ALK protein in the tumour. It has high sensitivity and specificity but positive results should be confirmed by FISH.

Having the test

Sample 
A sample of tumour tissue is obtained through a biopsy procedure or sometimes collected during surgery for tumour resection. The tumour tissue is typically first evaluated by microscopic examination by an anatomical pathologist prior to ALK testing.

Test preparation?
None

Your result

If the cancer tissue contains a specific ALK gene rearrangement mutation or altered ALK protein, then you are likely to benefit from an ALK kinase inhibitor drug therapy such as crizotinib and not likely to benefit from anti-EGFR drug therapies.
If your cancer does not have an ALK gene rearrangement you are not likely to benefit from ALK kinase inhibitor drug therapy.

It is possible that you could have a false negative test result if the tumour tissue sample is insufficient and/or when the cancer is heterogeneous – some cells contain the mutation and others do not. Also there are some rare ALK mutations that are not detected by routine testing that looks for only the most common mutations.

A different gene rearrangement where ALK is fused with the NPM gene may be seen in some T-cell lymphomas.

Any more to know?

ALK gene rearrangements are most often seen in light smokers or non-smokers with adenocarcinoma non-small cell lung cancers, especially in women of Asian descent. Although this is a relatively rare mutation, the total number of people affected by lung cancer each year means that the test and potential drug therapy is applicable to many people.

Most people whose lung cancer has the ALK gene rearrangement will respond to treatment, but a percentage will not. Each person and each cancer is different. Also, a person may respond initially and then become resistant to the treatment.

The ALK test must be performed on a sample of tissue – not a blood sample.  It is not the genetics of the person that is being evaluated, rather it is the genetic makeup of the cancer.

ALK mutation testing is available on Medicare and can be requested by a specialist in the investigation of non-small cell lung cancer in relation to access to crizotinib under the Pharmaceutical Benefits Scheme (PBS).  MBS item number 73341.

More information

Pathology and diagnostic imaging reports can be added to your My Health Record. You and your healthcare provider can now access your results whenever and wherever needed.
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