Stage II Colon Cancer Patients: Mismatch Repair Protein and Oncotype DX Testing

How do doctors know whether or not to provide chemotherapy to stage II colon cancer patients? Dr. George P. Kim explains the process, including testing mismatch repair proteins and microsatellite instability, and using the Oncotype DX test.

George P. Kim, MD: So, stage II patients are those individuals where their cancer is found invading into the wall but has not got into the lymph nodes. And this is a controversial area in terms of what we should do after they have undergone a potentially curative surgery should we give them chemotherapy. Now in general, it’s about 80% of patients that are cured and 20% of patients that are still at risk. That may be acceptable to some folks, but for us we want to try to cure everybody. So how do we improve upon those numbers, especially that 20%. We know the chemotherapy given the stage III patients provides about a 33% benefit so arguably of that 20% we can divide that by three. We push another six or seven patients into the cured group. The limitations with that, is that we have to treat everybody to get that extra six patients into the cured group. So, is there any test or any way to reevaluate that and identify who the patients are and I think we have done great work in trying to identify this and it is actually something we talked about earlier, the microsatellite instability, the defectiveness mismatch repair that underlies the hereditary nonpolyposis colorectal cancer genetic syndrome, Lynch syndrome. So, what does that all mean, there are specific DNA repair enzymes that are defective this leads to abnormalities throughout the genome, throughout the cancer genes that are what we call microsatellites, these genes are unstable, they are mutated. This raises the risk for colon cancer before the age of 50, but it also paradoxically leads to improved prognosis, so you have a better prognosis even though you are at risk for developing colon cancer.

Moving on into the context of treatment in a stage II patient, this marker it was concerned early on that patients who had this marker were going to be resistant to chemotherapy, for example to 5-FU, Fluorouracil, a drug that is the backbone of some of our chemotherapy combinations. This is supported in the lab and some data became available that suggested that patients with this marker do not benefit from this specific chemotherapy. So, this is a chemotherapy that we give stage II patients and here we have the potential that they do not going to benefit. So I think the conclusion is, if you have what they call microsatellite instability high, MSI, or defective mismatch repair, you have a good prognosis, you have potential harm from chemotherapy and for all those reasons I think what we do now, is we observe these patients, we do not subject them to chemotherapy. So, I think that’s the best answer that we have. We would not treat these individuals, we would just observe them because their prognosis is so good.

Other tests for stage II patients are being developed one of them is the Oncotype DX test. This is a very important test. It has validated numerous series, a large databases and basically what it tells us is that if you have a T4 lesion in the colon that is a tumor that is invaded through the wall and starting to invade other structures in the abdomen. If you have that type of lesion and I think we already knew this, you need to receive chemotherapy. As we said earlier, if you had microsatellite instability, MSI high, we would not treat you. But in the middle of those curves is what we call the T3, N0 patients about 74% and the Oncotype DX test enables us to have either a low risk, intermediate risk, or higher risk group identified and in my practice I tend to treat high risk patients, the lower the intermediate risk groups, I will not treat.

George P. Kim, MD is an Assistant Professor of Oncology, Mayo Clinic College of Medicine and is a consultant in the Department of Hematology and Oncology, Mayo Clinic Jacksonville.

****

This information should not be relied upon as a substitute for personal medical advice, diagnosis or treatment. Use the information provided on this site solely at your own risk.  If you have any concerns about your health, please consult with a physician.


This information should not be relied upon as a substitute for personal medical advice, diagnosis or treatment. Use the information provided on this site solely at your own risk. If you have any concerns about your health, please consult with a physician.

© 2022 Cancer Answers LLC