Tumor Screening for HNPCC (IHC/MSI)

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Tumor Screening for HNPCC (IHC/MSI)

What Is Tumor Screening for Hereditary Non-polyposis Colorectal Cancer?

About 2% to 5% of all colon cancers are caused by a genetic condition called hereditary non-polyposis colorectal cancer (HNPCC). Many people with HNPCC don't know that they have it. HNPCC is also called Lynch syndrome.

Although HNPCC is genetic, family history alone isn't very good for finding people with HNPCC. It is important to diagnose HNPCC because the risk for getting colon, endometrial, and certain other cancers is much higher than usual. People with HNPCC, and their family members, need extra testing to look for warning signs of cancer to prevent cancer or catch it early when treatment is most effective.

Learn more about HNPCC here

Tumors from people with HNPCC usually have certain characteristics that help point to HNPCC. Tumor screening tests, called immunohistochemistry or microsatellite instability, can find these HNPCC signs.

Immunohistochemistry
HNPCC usually causes one of four proteins to be missing in a tumor. Immunohistochemistry (IHC) uses special stains to see if these four proteins are in the tumor tissue. If any one of these proteins is missing, it can be a sign of HNPCC. Immunohistochemistry will find about 83% of HNPCC cases.

Microsatellite Instability
Cancer caused by HNPCC usually has changes in part of the DNA called microsatellites. Microsatellite instability (MSI) testing measures the amount of DNA changes in certain microsatellites. Tumors with many microsatellite changes have "high microsatellite instability" (written MSI-H). High microsatellite instability is a strong clue that HNPCC may have caused the tumor, but it isn't always the cause. Microsatellite instability testing will find 55% to 91% of HNPCC cases.

See How Testing Works for more information about these tests. Doctors may choose either of these two tests or they may do both. If either test shows signs of HNPCC, you should consider genetic testing to look for a gene change that causes HNPCC.

Next: Who Should Consider Tumor Screening for Hereditary Non-polyposis Colorectal Cancer?

Why are you considering tumor screening for HNPCC?

I have had colon cancer.

I have had endometrial cancer.

I have had another cancer that is more common with HNPCC (like small bowel, stomach, ovarian, pancreatic, kidney, biliary tract, or brain), but not colon or endometrial cancer.

I have not had cancer, but I have a family history of possible or definite HNPCC.

None of these

Tumor screening is the first test for people with colon cancer who are concerned it may be caused by HNPCC. Some doctors only recommend tumor screening for people with HNPCC risk factors, while others will offer screening to anyone with colon cancer. Talk to your doctor if you are unsure if you should consider tumor screening.

Two HNPCC tumor screening tests are available — immunohistochemistry (IHC) and microsatellite instability (MSI). If testing is needed, you and your doctor may choose to do one or both.

Both tests find a similar number of people with HNPCC; but the tests look for different signs of HNPCC and may find different people with the condition. So, it may be useful to do both. An important difference is that IHC gives clues about which gene may cause HNPCC, and MSI doesn't. Knowing which gene to test may save time and money if you need genetic testing.

If tumor screening is abnormal

An abnormal tumor screening result doesn't mean you have HNPCC, but it does increase the chance quite a bit. Your doctor will probably offer you genetic testing to look for a gene mutation that causes HNPCC. If you had an abnormal IHC test, those results will help your doctor figure out which gene(s) to test first. The first person tested usually has full gene sequencing, which looks at whole genes, "letter-by-letter," to find any change from normal. This kind of testing is expensive and time-consuming, but necessary to find as many different mutations as possible.

Finding an HNPCC mutation by genetic testing confirms a diagnosis. If genetic testing doesn't find a mutation, it doesn't rule out HNPCC because genetic testing cannot find all mutations that cause HNPCC.

If tumor screening is normal

Both MSI and IHC find most tumors caused by HNPCC. If you had only one of these tests and your doctor strongly suspects HNPCC, your doctor may suggest doing the other test next. When both are normal, HNPCC is unlikely and no further testing is usually recommended.

If you have a family history of cancer that might be explained by HNPCC, testing other family members may help find a diagnosis for your family. You should talk to your doctor or a genetic counselor about your family history. You can learn more about other kinds of testing in the HNPCC Genetic Testing area.

Tumor screening may be appropriate for women who have had endometrial cancer before 50 or who have certain other signs that their cancer was caused by HNPCC. However, this isn't as clear as it is for colon cancer. Tumor screening is not recommended for every woman with endometrial cancer. Talk to your doctor if you are unsure if you should consider tumor screening.

Two HNPCC tumor screening tests are available — immunohistochemistry (IHC) and microsatellite instability (MSI). If testing is needed, you and your doctor may choose to do one or both.

Both tests find a similar number of people with HNPCC; but the tests look for different signs of HNPCC and may find different people with the condition. So, it may be useful to do both. An important difference is that IHC gives clues about which gene may cause HNPCC, and MSI doesn't. Knowing which gene to test may save time and money if you need genetic testing.

If tumor screening is abnormal

An abnormal tumor screening result doesn't mean you have HNPCC, but it does increase the chance quite a bit. Your doctor will probably offer you genetic testing to look for a gene mutation that causes HNPCC. If you had an abnormal IHC test, those results will help your doctor figure out which gene(s) to test first. The first person tested usually has full gene sequencing, which looks at whole genes, "letter-by-letter," to find any change from normal. This kind of testing is expensive and time-consuming, but necessary to find as many different mutations as possible.

Finding an HNPCC mutation by genetic testing confirms a diagnosis. If genetic testing doesn't find a mutation, it doesn't rule out HNPCC because genetic testing cannot find all mutations that cause HNPCC.

If tumor screening is normal

Both MSI and IHC find most tumors caused by HNPCC. If you had only one of these tests and your doctor strongly suspects HNPCC, your doctor may suggest doing the other test next. When both are normal, HNPCC is unlikely and no further testing is usually recommended.

If you have a family history of cancer that might be explained by HNPCC, testing other family members may help find a diagnosis for your family. You should talk to your doctor or a genetic counselor about your family history. You can learn more about other kinds of testing in the HNPCC Genetic Testing area.

Most people with HNPCC have colorectal or endometrial cancer. Other cancers seem to be more common with HNPCC, but they don't point to HNPCC strongly enough to justify tumor screening in most cases. We also don't know how good tumor screening tests are for finding out if these other cancers are caused by HNPCC. So, tumor screening isn't usually recommended for other kinds of cancer.

If you have a strong family history of cancer that suggests HNPCC, your doctor or genetic counselor may suggest testing another family member. See the HNPCC Genetic Testing area for a more general discussion of HNPCC testing options.

Tumor screening for HNPCC is only appropriate for certain people who have had colon or endometrial cancer.

If you have a family history that suggests HNPCC, tumor screening for a relative who had colon or endometrial cancer is a good first step for finding out if HNPCC runs in the family. If no living relative is available, it may still be possible to do tumor screening on tissue that the laboratory has saved.

If tumor screening is abnormal, genetic testing can be done to look for a gene mutation that causes HNPCC in the family. If a mutation is found, then you and other family members can have testing for the one mutation that runs in the family. Testing for one mutation is much less expensive and more accurate than complete gene testing. If a mutation isn't found, then testing won't be useful for anyone else in the family.

See the HNPCC Genetic Testing area for a more general discussion of HNPCC testing options.

Tumor screening for HNPCC is only appropriate for certain people who have had colon or endometrial cancer. If you haven't had either of these kinds of cancer, this testing probably won't be useful for you.

Tumor screening by immunohistochemistry (IHC) or microsatellite instability (MSI) may be done for reasons other than looking for HNPCC. These reasons for tumor screening aren't covered here. If you had another reason to consider tumor screening, talk to your doctor or a genetic counselor about whether testing may help you.