RAS (KRAS and NRAS, all RAS) testing
The biopsy or resection specimen tissue are stored by the pathology laboratory for at least ten years. This means that the test can be undertaken on this “archive” material at any stage in the future if disease becomes evident at a different place in the body (metastatic disease).
Testing for RAS gene mutations has recently become very important in determining the best form of treatment for metastatic colon cancer. RAS is involved in passing signals within tumour cells which result in growth of the tumour (via the RAS-RAF-MAP kinase pathway). The gene which is responsible for RAS signalling occurs in two different forms; mutated (abnormal) and wild-type (normal).
Approximately 40% of patients with metastatic colon cancer have a tumour with a mutated RAS gene. These patients are unlikely to respond to treatment with anti-epidermal growth factor receptor therapies such as cetuximab and panitumumab. Treatment using these drugs is not recommended for patients with mutated RAS gene as they would suffer from unwanted side effects of the drug without getting any benefit.
Patients with metastatic disease who have normal (wild-type) RAS genes are likely to respond to either cetuximab or panitumumab.
In the UK, RAS gene testing is recommended in all patients with metastatic colorectal cancer. There is a good correlation between RAS gene mutation status in the primary tumour and metastases. Stored biopsies or resection specimens of the primary tumour taken months or years before the onset of metastatic disease can be tested for RAS gene mutation at a later date.
How is the sample collected for testing?
A sample of cancer tissue is obtained by doing a fine needle aspiration, needle biopsy, or surgical biopsy/excision
Is any test preparation needed to ensure the quality of the sample?
No test preparation is needed.
How is it used?
Patients with metastatic colon cancer and wild-type (normal) RAS gene status may be offered treatment with drugs such as cetuximab (Erbitux) and panitumumab (Vectibix). These drugs are known as epidermal growth factor receptor inhibitors. Those patients who have the mutant type of RAS gene will not derive benefit from treatment with these agents.
When is it requested?
RAS mutation testing is recommended as part of the workup of patients with metastatic colorectal cancer. It helps the doctor determine treatment options and understand more about the cancer’s characteristics.
What does the test result mean?
Patients whose tumours have a mutated RAS gene are unlikely to respond to treatment with anti-epidermal growth factor receptor therapy such as cetuximab and panitumumab. Patients with metastatic disease with wild-type (normal) RAS genes are likely to respond to these treatments, which improve the overall response to chemotherapy.
Besides RAS what other laboratory tests may my doctor request on my colorectal cancer tissue?
"All-RAS" testing (testing for both KRAS and NRAS) is currently the only additional test that oncologists will routinely request if metastatic disease is found.
If the tumour is RAS mutated, does this mean that the tumour will not respond to any chemotherapy?
No, tumours often respond to conventional chemotherapy. However, the improved response which is seen in some patients with the addition of epidermal growth factor receptor inhibitors will not be seen in patients with mutated RAS genes. This additional treatment is not indicated in patients with mutated RAS genes.