Microsatellite stability biomarker (MSS) and colorectal cancer
Your microsatellite status is an important biomarker that can help you and your healthcare team better understand your colorectal cancer and identify treatment options that may be appropriate for you.
What is an MSS biomarker?
MSS stands for microsatellite stability, sometimes described as microsatellite stable.
Microsatellites are short, repeated sections of DNA. Healthy cells have a process called mismatch repair, or MMR, that identifies and corrects certain mistakes that occur when DNA is copied.
Testing can show whether the DNA within a colorectal cancer tumor is:
- Microsatellite stable, or MSS: The tumor has relatively few errors in its microsatellites and usually has a functioning mismatch repair system. This may also be reported as mismatch repair proficient, or pMMR.
- Microsatellite instability-high, or MSI-H: The tumor has a high number of microsatellite changes and often has a deficient mismatch repair system, or dMMR.
A tumor is generally classified as either MSS/pMMR or MSI-H/dMMR. These results help doctors understand the biology of the cancer and determine which treatments should be considered.
How common is MSS colorectal cancer?
Approximately 80% to 85% of colorectal cancers are classified as MSS. Because MSS tumors represent most colorectal cancers, developing more effective treatments for this group remains a major area of research.
Approximately 15% of colorectal cancers are MSI-H or dMMR. In some patients, an MSI-H or dMMR result may be associated with Lynch syndrome, an inherited condition that increases the risk of colorectal cancer and several other cancers.
In 3% to 5% of colorectal cancer patients, dMMR and MSI-H are caused by Lynch syndrome. In these patients, a hereditary mutation (germline mutation) in one of the four main MMR genes is passed from one generation to another in a family. Individuals with Lynch syndrome are at higher risk of developing colorectal, endometrial (uterine), gastric, ovarian, and other cancers.
Who should have MSS testing?
Microsatellite instability or mismatch repair testing is recommended for everyone diagnosed with colorectal cancer.
Testing may be completed using a sample of tumor tissue obtained during a biopsy or surgery. Ask your healthcare team whether your tumor has been tested and request a copy of your biomarker testing results.
What does an MSS result mean?
An MSS result is one piece of information used to develop a personalized treatment plan. It does not, by itself, determine every treatment you may receive.
Patients diagnosed with an MSS tumor have a higher risk of recurrence. If you have advanced or metastatic colorectal cancer, your healthcare team may also test for biomarkers such as:
- KRAS and NRAS
- BRAF
- HER2
- NTRK
- Tumor mutational burden, or TMB
- Other biomarkers that may help guide treatment or clinical trial eligibility
The biomarkers that should be tested can depend on the stage of your cancer, previous treatments and the amount of tumor tissue available.
Treatment options and potential side effects
Treatment depends on several factors, including the cancer’s stage, where it is located, whether it has spread, other tumor biomarkers, treatments you have already received, and your overall health and preferences.
Treatment for MSS colorectal cancer may include:
- Surgery
- Chemotherapy
- Radiation therapy in certain situations
- Targeted therapies for tumors with specific biomarkers
- Liver-directed or other localized treatments when appropriate
- Clinical trials evaluating new treatment approaches
Your healthcare team can explain the potential benefits and risks of each option and help you understand how your MSS status and other biomarkers affect your treatment plan. There are ongoing clinical trials for immunotherapy in combination with different drugs for MSS patients.
Some of the most common side effects of treatment for patients with MSS tumors are nausea, fatigue, diarrhea or constipation, headaches, and high temperature.
It is unlikely that you will have all of these side effects, but you might have some of them. Contact your doctor immediately if you are experiencing severe symptoms.
Emerging research and the changing treatment landscape
For many years, systemic treatment options for people with MSS colorectal cancer have relied primarily on chemotherapy and, when appropriate, targeted therapies.
Immunotherapy has changed the treatment landscape for some people with colorectal cancer, particularly those whose tumors are MSI-H or dMMR. However, standard immune checkpoint inhibitors used alone have generally not been effective for most MSS colorectal cancers.
This may be partly because MSS tumors often have characteristics that make it more difficult for the immune system to recognize or attack them. Cancer cells can avoid immune responses in several ways, including becoming less visible to immune cells or creating conditions around the tumor that suppress immune activity. Researchers are studying combinations and new treatment approaches intended to overcome this resistance.
Having an MSS tumor does not mean that immune-based research or clinical trials are not options. Researchers are actively exploring ways to help the immune system better recognize MSS tumors and produce stronger, more lasting treatment responses.
New approaches being studied
Researchers are evaluating several approaches for MSS colorectal cancer, including combinations of immunotherapy with targeted treatments, chemotherapy, radiation, and other immune-based therapies.
One area of research involves bispecific antibodies.
Traditional antibodies generally recognize one specific target. Bispecific antibodies are created in a laboratory and designed to bind to two different targets at the same time. Depending on how a bispecific antibody is designed, it may target two signals involved in cancer growth or bring an immune cell close to a cancer cell so the immune cell can attack it more effectively.
In MSS colorectal cancer research, bispecific antibody approaches may be designed to:
- Help immune cells recognize and attack cancer cells
- Block signals that help tumors grow or avoid the immune system
- Change the environment surrounding the tumor
- Help another immune-based treatment work more effectively
Other investigational approaches include cancer vaccines, cell therapies, and drugs that target different parts of the immune response or tumor environment.
These approaches are still being evaluated. Participation in a clinical trial may provide access to an investigational treatment, but it does not guarantee that the treatment will be safe or effective.
Why clinical trials matter for MSS colorectal cancer
Clinical trials are essential to developing more effective treatments for MSS colorectal cancer. Researchers use clinical trials to determine whether a new treatment or treatment combination is safe, how it should be given, and whether it works better than existing options.
Clinical trials may be available at different points in care, including:
- Before a patient begins their first treatment
- After an initial treatment has stopped working
- During later lines of treatment
- Before or after surgery in certain research settings
Considering a clinical trial early can give you and your healthcare team more time to review possible studies. You do not need to wait until all standard treatments have been used to ask about clinical trials.
Eligibility may depend on:
- The stage and location of your cancer
- Treatments you have already received
- Your MSS status and other tumor biomarkers
- Your overall health
- The study’s specific eligibility requirements
- Your treatment needs and goals
Clinical trial participation is voluntary. Before enrolling, the research team should explain the study’s purpose, possible benefits, known and unknown risks, required tests, treatment schedule, and potential costs. Clinical trials also have safeguards intended to protect participants, including informed consent and independent review.
Questions to ask your healthcare team
- Has my tumor been tested for MSS, MSI and mismatch repair status?
- Have I received comprehensive biomarker testing?
- How do my biomarker results affect my treatment options?
- Are clinical trials available for my type and stage of colorectal cancer?
- Should I consider a clinical trial now or at another point in treatment?
- Would a second opinion from a colorectal cancer specialist be helpful?
What does this mean for patients?
An MSS result provides important information about your tumor, but it does not define every treatment opportunity available to you.
Although standard immune checkpoint inhibitors used alone have generally not worked well for most MSS colorectal cancers, researchers are actively studying new therapies and combinations designed specifically to address the biology of MSS disease.
Ask your healthcare team to review all of your biomarker results—not only MSS status—and discuss standard treatments, targeted therapies, and clinical trials that may be appropriate for you.
The goal of ongoing research is to create more effective treatment options and help more people with colorectal cancer benefit from advances in personalized and immune-based cancer care.
Find support and clinical trials
Use the Alliance Personalized Oncology Care Application to connect with the Cancer Care Team for help understanding and exploring possible clinical trial options.
You don’t have to do this alone. Call the Colorectal Cancer Alliance Helpline at (877) 422-2030.
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