Microsatellite Instability-High (MSI-H) Colon Cancer Symptoms, Causes, Treatment

Written by Stephanie Watson
Medically Reviewed by Laura J. Martin, MD on May 15, 2025
11 min read

Microsatellite instability-high (MSI-H) colon cancer is when colon cancer cells have DNA mistakes called mutations that can't be fixed. This makes them very unstable. Microsatellites are short sections of DNA in cells that repeat over and over. 

Normally, when cancer cells divide to make new cells, their DNA copies itself. A process called mismatch repair (MMR) constantly scans for any mistakes in the DNA copies and fixes them. If MMR doesn't work, each time the DNA copies itself, the mistakes get copied, too, and they make the cancer cells unstable. The name for a problem with the cell's DNA repair system is deficient DNA mismatch repair, or dMMR.

Instability is actually a good thing. MSI-H may respond better to immunotherapy and have a better outlook than microsatellite stable (MSS) colon cancer. 

What is the microsatellite instability biomarker?

The microsatellite instability biomarker is a substance in your colon cancer cells that your doctor can test to see if you have MSI-H. The cells come from the sample taken during a biopsy. Testing for the MSI biomarker helps your doctor make treatment decisions and figure out your outlook.

MSI-H colon cancer doesn't always cause symptoms. When there are symptoms, the most common ones are:

  • A change in your poop habits, like diarrhea, constipation, or a feeling like you need to poop after you just went to the bathroom
  • Blood in your poop that looks dark brown or black
  • Bleeding from your rectum that is bright red
  • Belly pain or cramps
  • Bloating

Having symptoms like these doesn't always mean you have MSI-H colon cancer. Many other diseases cause the same symptoms. But it's important to see your doctor soon if you have bleeding from the rectum,  blood in your stool, or severe abdominal (belly) pain. If you have a change in your poop habits or bloating symptoms that go on for more than two weeks, you should talk with your doctor.

What's the first sign of MSI-H colon cancer?

A low red blood cell count on a blood test is sometimes the first sign of MSI-H colon cancer. Bleeding in the colon causes a drop in red blood cells, which is called anemia. It's one of the most common symptoms, affecting 30% to 75% of people with colon cancer.

Other MSI-H colon cancer symptoms

MSI-H colon cancer causes symptoms like these when it spreads to organs such as the liver, lungs, or brain:

  • Tiredness
  • Yellow skin and whites of the eyes (jaundice)
  • Nausea
  • Reduced appetite
  • Weight gain or loss
  • Swelling in the arms or legs
  • Shortness of breath or trouble breathing
  • Chest pain
  • Cough that doesn't go away
  • Headaches
  • Confusion 
  • Blurred vision

Gene mutations cause colon cancer. In most cases of MSI-H, the change is to one of the DNA mismatch repair (MMR) genes in a cancer cell, the mutation happens during your lifetime, and the cause is not known.

As many as 5% of people with colon cancer have an inherited condition called Lynch syndrome. The MMR gene mutation is passed down through their family to them. Having Lynch syndrome puts you at a higher risk of colon cancer.

Certain lifestyle factors also make you more likely to get colon cancer. 

These risks are not under your control:

  • Age (over 50)
  • A personal or family history of colorectal cancer
  • An inherited condition like Lynch syndrome or familial adenomatous polyposis (FAP)
  • Polyps in your colon
  • Ashkenazi Jewish, American Indian, or Alaska Native heritage
  • Ulcerative colitis or Crohn's disease 
  • Radiation to the belly or pelvis

These are risks you can do something about:

  • Obesity 
  • Type 2 diabetes
  • Tobacco smoking
  • Alcohol use
  • A diet high in red meat and processed meat

How common is it?

About 154,000 new cases of colorectal cancer are diagnosed in the United States each year. Around 15%, or 23,000, of those cancers are MSI-H. 

If a doctor suspects you have colon cancer based on your symptoms and medical history, they'll order tests. A colon cancer diagnosis may involve blood tests, a colonoscopy, biopsy, and imaging scans.

Tests for MSI-H colon cancer

These tests detect colon cancer:

  • Colonoscopy uses a flexible tube with a light and video camera to view the rectum and colon. Your doctor can do a biopsy during a colonoscopy, removing a small piece of tissue from your colon to test.
  • Molecular tests check for gene changes in the biopsy sample.
  • Imaging tests like computed tomography (CT), ultrasound, X-ray, magnetic resonance imaging (MRI), and positron emission tomography (PET) can show whether the cancer has spread to other organs.

To find out if you have MSI-H colon cancer, a lab will check for the MMR genes in your biopsy sample using tests like these: 

  • Immunohistochemistry (IHC) looks for proteins called antigens in a tissue sample.
  • Polymerase chain reaction (PCR) makes many copies of a small piece of DNA to diagnose genetic disorders.
  • Next-generation sequencing (NGS) quickly analyzes large amounts of DNA for mutations.

What to know when you're first diagnosed

A cancer diagnosis can be overwhelming. You have so much to process and learn. Take time to find a doctor you trust, ask a lot of questions, and find out as much as you can about the cancer and its treatment. If you're unsure about anything, ask for a second opinion.

Treating colon cancer involves a team of specialists. You may see a:

  • Gastroenterologist – a doctor who treats diseases of the GI tract
  • Surgical oncologist or colorectal surgeon – a doctor who treats colon cancer with surgery
  • Medical oncologist – a doctor who prescribes medicines like immunotherapy and targeted therapy to treat colon cancer

These are some of the other health care providers who may be involved with your treatment: 

  • Physician assistant
  • Nurse practitioner
  • Nurses
  • Genetic counselor
  • Mental health care providers such as a psychologist and social worker
  • Dietitian

Questions to ask your doctor

These questions can help guide the conversation with your colon cancer doctor:

  • What stage is my cancer?
  • How will microsatellite instability affect my choice of treatments?
  • Does my cancer have any other gene changes?
  • What treatments do you recommend and why are you recommending them?
  • What are the benefits and risks of the treatment?
  • Should I see a genetic counselor?
  • What is my prognosis?

The choice of therapy depends on things like the stage of your cancer – how far and where it has spread. Surgery and medication are the main treatments for MSI-H colon cancer.

Surgery for MSI-H colon cancer

Surgery is usually the first treatment for colon cancer that hasn't spread. The type of surgery you have depends on the size and location of the cancer.

  • A polypectomy takes out the tumor with the polyp it's attached to.
  • A local excision removes the cancer and a small amount of tissue around it.
  • A partial colectomy takes out part of the colon.
  • A total colectomy removes the entire colon.

Medication treatments for MSI-H colon cancer

Immunotherapy drugs called checkpoint inhibitors are an important part of treatment for both early- and late-stage MSI-H colon cancer. Checkpoints are proteins on the surface of immune cells. They turn on to attack germs and cancer and turn off to avoid harming healthy cells. Cancer sometimes uses checkpoints to protect itself from the immune system.

Dostarlimab (Jemperli), nivolumab (Opdivo), and pembrolizumab (Keytruda) are PD-1 inhibitors. These medicines block a checkpoint protein called PD-1 to boost the immune system response against MSI-H colon cancer. Ipilimumab (Yervoy) is a CTLA-4 inhibitor that blocks CTLA-4 protein and boosts the immune system.

Chemotherapy uses strong drugs to kill cancer cells. Doctors use it to shrink colon cancer before surgery, kill cancer cells that were left behind after surgery, and treat cancer that has spread to other organs.

Targeted therapy blocks certain substances that help colon cancer cells grow, including: 

  • New blood vessels (anti-VEGF medicines)
  • Abnormal proteins like epidermal growth factor receptor (EGFR), HER2, BRAF, TRK, RET, or KRAS

Natural or alternative treatment for MSI-H colon cancer

Natural treatments won't cure colon cancer, but therapies like these used along with cancer treatment might improve your quality of life:

  • Acupuncture helps with nausea, vomiting, constipation, diarrhea, and pain.
  • Aromatherapy eases stress and anxiety.
  • Massage helps with sleep, pain, fatigue, and anxiety.
  • Meditation and yoga reduce stress.

Ask your doctor before you try any alternative therapy, to make sure it's safe for you.

Stages of MSI-H Colon Cancer

Colon cancer stages go from 0 to IV. The lower the number, the less the cancer has spread.

Stage 0 has not grown beyond the inner lining of the colon.

Stage I is only in the inside layers of the colon. About 20% of all stage I colon cancers are MSI-H.

Stage II has grown into the outer layers or through the muscle wall of the colon. Around 20% of stage II colon cancers are MSI-H. 

Stage III has spread to the lymph nodes. About 12% of stage III colon cancers are MSI-H.

Stage IV has spread to one or more distant organs, like the liver or lung. About 4% of stage IV colon cancers are MSI-H.

Complications happen as the cancer grows. The tumor can block the colon, spread to other organs like the liver or lung, or come back after treatment. MSI-H colon cancer may be less likely to spread or to come back after surgery than other types of colon cancer.

Taking care of your physical and mental health is important when you have MSI-H colon cancer. A healthy diet, exercise, and emotional support can help you feel better during treatment.

MSI-H colon cancer diet

It takes time for your colon to recover after surgery. Until your intestines are fully working again, certain foods could cause gas and diarrhea. You may want to avoid foods like these if they bother you:

  • Raw fruits and vegetables with their skins on, especially vegetables like cabbage and Brussels sprouts
  • Whole-grain breads and cereals
  • Beans and lentils
  • Soda, beer, and other carbonated beverages
  • Fatty or rich foods

These are some other dietary tips for colon cancer:

  • Eat foods that are high in protein, like fish, tofu, chicken, eggs, and lean meat, to help you regain strength.
  • Cut down on high-fiber foods.
  • Avoid processed meats like bacon and salami, and highly refined grains such as white bread and cookies.
  • Drink extra fluids to stay hydrated.
  • If you don't have much of an appetite, eat several smaller meals throughout the day instead of three big ones.
  • Eat slowly to prevent gas.

MSI-H colon cancer cost

Checkpoint inhibitor drugs very work very well against MSI-H colon cancer, but they're expensive. A one-month supply of these drugs can cost as much as $15,000. Even with health insurance, copays and deductibles can lead to high out-of-pocket costs.

The social worker or patient navigator at your cancer hospital can tell you about programs and services to make your medicines cost less. Organizations like these offer financial assistance for cancer treatment:

  • Patient Advocate Foundation (PAF)
  • Cancer Financial Assistance Coalition (CFAC)
  • HealthWell Foundation
  • Colorectal Cancer Alliance
  • CancerCare

Tips for living with MSI-H colon cancer

Here are some ways to care for yourself during treatment for MSI-H colon cancer:

  • Eat a nutritious diet. A dietitian can give you advice on which foods to eat and which ones to avoid.
  • Exercise can help you feel better, and it may improve colon cancer survival. Stay active by doing aerobic exercises like walking, bike riding, and yoga. After surgery, ask your doctor how soon you can start exercising. You may need to avoid lifting anything heavy for at least the first six weeks after your surgery.
  • Treat your symptoms. Ask your doctor about palliative care – a program to manage pain and other symptoms. Palliative care works along with your treatment, not instead of it.
  • Get support from your medical team, friends and family, and a colon cancer support group.

MSI-H colon cancer and mental health

Having cancer can be very stressful. It's normal to feel anxious, overwhelmed, or sad. Research finds that having colon cancer puts you at a higher risk of mental health conditions like depression and anxiety.

It's just as important to care for your mental health as your physical health. Here are some tips that might help:

  • Don't keep your emotions bottled up inside. Talk with friends, family, a counselor, or a support group. 
  • Relax and unwind. Take a walk, meditate, practice yoga, or watch one of your favorite movies. 
  • Do things you enjoy. Take time for hobbies like painting, photography, or music.
  • Become an active part of your own care. Advocating for yourself will make you feel more in control of your own health.

Support for MSI-H Colon Cancer

These organizations offer resources and support for people with colon cancer:

  • Colorectal Cancer Alliance
  • Colontown
  • CancerCare
  • American Cancer Society

The five-year survival rate for colon cancer ranges from 91% for an early-stage cancer to 13% for a cancer that has spread to other organs. MSI-H colon cancers tend to respond better to treatments like immunotherapy. They may have a better outlook than microsatellite stable colon cancers, especially when the cancer is diagnosed at an early stage. 

Can MSI-H colon cancer be cured?

Early-stage MSI-H colon cancer is very treatable. Surgery and medicine can lead to remission, which is when you have no more signs or symptoms of cancer. It's possible for cancer to come back after treatment, but your care team will monitor you regularly for a recurrence.

What to expect with MSI-H colon cancer

Everyone with colon cancer is different. Survival rates only estimate what will happen to large groups of people. They can't predict your outcome. Your doctor can give you a better idea of your prognosis based on your cancer stage, health, and how well you respond to treatment.

MSI-H colon cancer cells contain DNA changes that make them unstable. These cancers respond very well to immunotherapy. Early-stage MSI-H colon cancers often have a good outlook. 

How is MSI-H found?

Doctors find MSI-H by testing a biopsy sample using a technique like PCR or IHC.

How common is MSI-H in colon cancer?

About 15% of all colon cancers are MSI-H.

What are the risk factors for MSI-H colon cancer?

Gene mutations cause MSI-H colon cancer. Sometimes these mutations pass down through families. Others happen spontaneously. Having an inherited condition like Lynch syndrome increases your risk. Increased age, excess body weight, smoking, and eating a lot of red and processed meats are other colon cancer risk factors. 

What is the difference between MSI-H and dMMR?

MSI-H stands for microsatellite instability-high. It means the cells have a lot of mutations in short, repeated pieces of DNA called microsatellites. dMMR stands for deficient DNA mismatch repair. It means the cell's DNA repair system isn't working.

Does MSI-H status affect treatment options?

Yes. MSI-H colon cancers respond especially well to immunotherapy drugs called checkpoint inhibitors.

Is the prognosis better or worse for MSI-H colon cancer? 

The prognosis may be slightly better for MSI-H colon cancer, especially when it's caught early.