Biomarker Testing for Colorectal Cancer

What are colorectal cancer biomarkers?

Biomarkers are substances in blood, tumor or other tissue that can give doctors clues for treating cancer. Testing for biomarker are performed in a lab. Biomarker tests that are performed on blood are sometimes called liquid biopsies. The results may help doctors understand: 

• how fast the cancer is growing
• which treatments are most likely to work
• whether or not the cancer is responding to treatment or growing
• whether or not the cancer has come back after remission

How are colorectal cancer biomarkers used?

Biomarker tests may be used to select treatments, figure out if a current treatment is working, look for early signs of recurrence, and to help patients avoid side effects from treatments that will not work for them. See our colorectal cancer treatment page for information on the treatments available based on biomarker test results. 

All colorectal cancers should be tested for microsatellite instability and mismatch repair deficiency

Experts recommend testing all colorectal cancers for biomarkers known as “microsatellite instability" and, or "mismatch repair deficiency" (dMMR or MMR-D). These biomarkers measure how well the tumor can repair certain types of DNA damage. The results have similar meaning. 

• Microsatellite instablity results are reported as MSI-H (microsatellite instability high), MSI-L (microsatellite instability low) or MSS (microsatellite stable). 
• Mismatch repair results are reported as dMMR or MMR-D (mismatch repair deficient) or pMMR or MMR-P (mismatch repair proficient).
• MSI-high and dMMR cancers are common in people with a Lynch syndrome gene mutation.
• People with advanced or metastatic MSI-high colorectal cancer may respond well to a type of immunotherapy known as an immune checkpoint inhibitor. 

Biomarkers used in advanced colorectal cancer

Experts recommend testing metastatic colorectal cancers for the following biomarkers to help guide treatment selection:

• Mutations in a gene known as RAS (KRAS and NRAS). 
• A specific mutation in a gene known as BRAF. 
• HER2 (also known as HER2/neu). Tumors that have this biomarker are known as HER2-positive. These tumors may respond well to a type of targeted therapy known as anti-HER2 therapy. 
• Additional biomarker tests may be used in colorectal cancer:
  • A biomarker known as an NTRK fusion is rare in colorectal cancer. People with advanced/metastatic colorectal cancer with an NTRK fusion may benefit from the targeted therapy Vitrakvi (larotrectinib).
  • Additional tumor biomarker testing may help people learn if they are eligible for certain clinical trials. 

BRAF V600E mutations
BRAF is a gene that helps control how cells grow and divide. A specific mutation called BRAF V600E can drive colorectal cancer growth and biomarker testing for this change is important because it identifies people who may benefit from targeted treatments designed specifically for this mutation. 

RAS biomarkers (KRAS and NRAS)
KRAS and NRAS are part of a group of genes known as the RAS pathway. RAS genes  help control how cells grow and divide. Changes (mutations) in these genes are common in colorectal cancer and are important because they affect which targeted treatments are likely—or unlikely—to work.

RAS wild-type or RAS mutation negative and EGFR-positive
Colorectal cancers that do not have mutations in either KRAS or NRAS are called RAS wild‑type. People with RAS wild‑type tumors may benefit from some targeted therapies.

KRAS G12C mutation
KRAS G12C is one specific type of KRAS mutation. Cancers that have KRAS G12C can be directly targeted with certain newer drugs, making it an important biomarker to test for in people with metastatic colorectal cancer. 

HER2-positive
Anti-HER2 therapies are used for people with advanced colorectal cancer when tumor testing shows a biomarker called HER2-positive.

NTRK gene fusions
NTRK gene fusions are biomarkers that are rarely found in colorectal cancer. Targeted therapies may be used for different types of advanced cancers (including colorectal cancer) with NTRK gene fusions that have gotten worse, stopped responding or came back after other treatments.   

RET gene fusions
RET gene fusions are biomarkers that are rarely found in colorectal cancer. Targeted therapies may be used for different types of advanced cancers (including colorectal cancer) with RET gene fusions that have gotten worse, stopped responding or came back after other treatments.    

Other biomarkers
Researchers are studying new biomarkers to improve treatment outcomes for people with  colorectal cancer. See the research section below for more information.

Does insurance cover the cost for colorectal biomarker testing?

Most private health insurers cover MSI or dMMR testing in patients with colorectal cancer who meet established medical criteria. Insurers may cover the cost for additional biomarker testing, especially in people with advanced cancers, however, out-of-pocket costs may vary depending on the type of test. Visit our sections on insurance and reimbursement for more information.