MSI Testing in Appendix Cancer: The Rare 3% That Matters

MSI testing in appendix cancer returns a high-instability result, written MSI-high, in only about 3 percent of appendiceal adenocarcinomas. That is far below the rate in colorectal cancer. Ruling it out is still worth doing, and so is knowing what to do if two different tests give you two different answers.

MSI testing in appendix cancer is something most patients never hear about, and there is a reason for that. An MSI-high result is rare in this disease, so the test usually changes nothing. For the small number of people whose result does come back MSI-high, it can open a treatment option and raise a question about the rest of the family.

Below is what the test measures, how often it turns up MSI-high, what happens when the results conflict, and why the answer is worth having even when it is likely to be negative.

What MSI and dMMR actually mean

Your cells have a built-in spell-check system that fixes small mistakes when DNA copies itself. The genes that run that system are called mismatch repair genes. When the system is working normally, the tumor is usually microsatellite stable, often written as MSS. When it stops working, mistakes pile up in short repeated stretches of DNA called microsatellites. A tumor like that is called microsatellite instability-high, or MSI-high, and the underlying breakdown is called mismatch repair deficient, or dMMR.

MSI-high and dMMR point at the same underlying problem, but they are measured in two different ways. MSI testing reads the DNA repeats directly. MMR testing checks whether four repair proteins, MLH1, PMS2, MSH2 and MSH6, are still present in the tumor tissue, using a method called immunohistochemistry. A pathologist can run either one on tumor tissue you have already given.

How often MSI testing in appendix cancer comes back MSI-high

This is where appendix cancer differs from its better-known neighbor. Across colorectal cancers overall, MSI-high shows up in roughly 15 percent of tumors, and in at least 20 percent of right-sided ones, which is why testing is routine there.

In the appendix it is far less common. An MD Anderson series of 108 appendiceal carcinomas found 3 MSI-high cases, or 2.8 percent. A much larger National Cancer Database analysis of 1,681 patients with known MSI status found 53 MSI-high tumors, about 3.2 percent.

The wording on your report matters here. In that same database analysis, 211 patients, or 12.5 percent, were recorded as MSI-positive in some form. Most of those were MSI-low or were not specified further. Only the 53 MSI-high cases fall into the group where a checkpoint inhibitor is usually discussed. So if a report says MSI-positive, ask which category it means.

One subtype note worth having. Goblet cell adenocarcinoma has generally been described in the literature as mismatch repair proficient and microsatellite stable. A 2026 case report from Tokyo documented what its authors describe as the first appendiceal GCA with both dMMR and MSI-high status. One case does not change the general picture, but it is a reason not to assume the answer for any single person based on subtype alone.

When the two tests do not agree

Most of the time the two results match. Sometimes they do not. Published colorectal cancer studies put the disagreement rate between MMR protein testing and molecular MSI testing at roughly 3 to 10 percent. Comparable numbers for appendiceal cancer specifically have not been established.

The scale of it shows up in trial data. In the CheckMate 8HW colorectal cancer trial, 303 patients were enrolled into the first-line comparison based on testing at their own hospital. When a central laboratory checked, 255 of them had confirmed MSI-high or dMMR tumors. That leaves roughly one in six whose local result was not confirmed centrally.

This is worth knowing because the two results can pull toward different treatments. A tumor can show missing repair proteins on the MMR test and still come back microsatellite stable with a low mutation count, and in that situation immunotherapy may not do what the MMR result alone would suggest. Ando and colleagues describe exactly that sequence in a 2026 preprint on appendiceal signet ring cell adenocarcinoma. I wrote it up separately in appendix cancer biomarker testing, including what her team did next.

If your reports show one result and not the other, or the two do not line up, that is a reasonable thing to raise with your oncologist rather than something to sort out on your own.

Why MSI testing in appendix cancer is still worth doing

In the United States, pembrolizumab carries an FDA tumor-agnostic indication for unresectable or metastatic MSI-high or dMMR solid tumors, identified by an FDA-authorized test, in patients whose disease has progressed after prior treatment and who have no satisfactory alternative options. An MSI-high result can therefore put an already-approved drug within reach without waiting for a trial slot, though whether it applies to you depends on your stage and what treatment you have already had. Approvals differ outside the U.S., so ask your own team what applies where you are treated.

The result can also point at Lynch syndrome, an inherited condition that raises the risk of several cancers. It does not mean you have Lynch syndrome. Most MSI-high tumors are not inherited at all, and in colorectal cancer the most common cause is a chemical change to the MLH1 gene that happens in the tumor itself rather than something passed down. What an MSI-high result can do is give a reason to consider genetic counseling and germline testing. If Lynch syndrome is confirmed, that information reaches your relatives, because it can change what screening they should have and when. Our post on appendix cancer genetic testing walks through what germline testing adds.

What a microsatellite stable result means

For most people with appendix cancer, especially low grade or mucinous disease, the tumor will be microsatellite stable. That is what the biology of this disease usually looks like, and it says nothing about the quality of your care or whether something was missed.

A stable result means MSI and MMR status are unlikely to give a standard reason to use checkpoint immunotherapy. It does not mean immunotherapy could never come up for you in any form, because trials, combinations, and other biomarkers exist and your situation is your own. MSI testing in appendix cancer is worth doing precisely because it tells you, one way or the other, which group you are in.

What to ask your care team

Ask whether your tumor has been tested for MMR or MSI, and what the result showed. If the answer is MSI-positive, ask whether that means MSI-high, MSI-low, or unspecified. If only one of the two tests was run, ask whether that result is enough on its own or whether there is a reason to run the other one as well. And if the two results conflict, ask whether the testing should be reviewed or repeated before it drives a treatment decision.

Already enrolled and need to add a new report or fix an earlier entry? Use the registry update form. If you want to help fund this work, you can give here.

Sources

Taggart MW, Galbincea J, Mansfield PF, et al. High-level microsatellite instability in appendiceal carcinomas. American Journal of Surgical Pathology. 2013;37(8):1192-1200. https://doi.org/10.1097/PAS.0b013e318282649b

Emile SH, Horesh N, Garoufalia Z, et al. The prognostic impact of microsatellite instability on the outcome of appendiceal adenocarcinoma: a National Cancer Database analysis. Journal of Gastrointestinal Surgery. 2023;27(2):354-362. https://doi.org/10.1007/s11605-023-05586-z

Hashimoto H, Koda H, Nakajima K, et al. Appendiceal goblet cell adenocarcinoma with mismatch repair deficiency and microsatellite instability-high status: a novel molecular signature guiding immuno-oncology strategy. Pathology International. 2026;76(3):e70108. https://doi.org/10.1111/pin.70108

Evrard C, Tachon G, Randrian V, Karayan-Tapon L, Tougeron D. Microsatellite instability: diagnosis, heterogeneity, discordance, and clinical impact in colorectal cancer. Cancers. 2019;11:1567. https://doi.org/10.3390/cancers11101567

Andre T, Elez E, Van Cutsem E, et al. Nivolumab plus ipilimumab in microsatellite-instability-high metastatic colorectal cancer. New England Journal of Medicine. 2024;391(21):2014-2026. https://doi.org/10.1056/NEJMoa2402141

Ando T, Tajiri Y, Noda Y, et al. Comprehensive genomic profiling-guided treatment selection in appendiceal adenocarcinoma with discordant mismatch repair findings. Research Square preprint, posted August 28, 2026. Not peer reviewed. https://doi.org/10.21203/rs.3.rs-10434247/v1

KEYTRUDA (pembrolizumab) prescribing information, label updated July 10, 2026. DailyMed, U.S. National Library of Medicine. dailymed.nlm.nih.gov

This post is patient education from Appendicure and is not medical advice. Testing and treatment decisions should be made with your own care team.