Study: Colorectal cancer in people with Lynch syndrome can include types of cancer found more typically in people without Lynch syndrome
Summary
When people with Lynch syndrome (LS) develop cancer, their tumors typically have a related set of features or biomarkers known as deficient mismatch repair (dMMR) and high microsatellite instability (MSI-High). However, occasionally people with Lynch syndrome have cancers that are proficient in mismatch repair (pMMR or MMR-P) and have microsatellite stability (MSS or MSI-Low) –more like the colorectal cancers found in people without Lynch syndrome. This study shows that 10 percent of people with Lynch syndrome may have these types of cancers. This can change treatment recommendations. (Posted 9/5/24)
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RELEVANCE
Most relevant for: People with Lynch syndrome and people with colorectal cancer who may have Lynch syndrome.
It may also be relevant for:
- people with colorectal cancer
- people with a family history of cancer
- people with a genetic mutation linked to cancer risk
- previvors
Relevance: Medium-High
Strength of Science: Medium-High
What is this study about?
This study looked at characteristics of colorectal cancers among people with . People with are most likely to have tumors with two related biomarkers: deficient mismatch repair or (also called ) and high (). These biomarkers are important because they can predict whether a tumor is likely to respond to treatment with . Researchers asked what percentage of colorectal cancer patients with do not have these biomarkers. That is, how often do people with have cancers that are mismatch repair proficient (pMMR) or are microsatellite stable (also called MSS). These cancers may need to be treated differently.
Why is this study important?
This study shows that people with may occasionally have colorectal cancers that are pMMR. Knowing whether a cancer is or pMMR may help to select which treatments might be most beneficial. This information could also influence family screening recommendations. If a person with has a pMMR colorectal cancer, their family members who are negative for would still be considered to have a family history of colorectal cancer.
Study findings
and any cancer
From a large study of 17,617 people with many types of cancer, 242 had an in one of the genes, meaning they had .
| gene | LS and any cancer (242 people) |
| MSH2/EPCAM | 86 of 242 (36%) |
| 57 of 242 (24%) | |
| 50 of 242 (21%) | |
| 49 of 242 (20%) |
Lynch syndrome-associated colorectal cancer
Among 242 people with cancer and , 86 had at least one colorectal cancer. A total of 99 colorectal cancers were evaluated in this study.
| gene | LS and colorectal cancer |
| MSH2/EPCAM | 35 of 99 (35%) |
| 30 of 99 (30%) | |
| 19 or 99 (19%) | |
| 15 of 99 (15%) |
Most but not all tumors in people with are
Researchers used two tests to test colorectal tumors for or pMMR. One test looked at tumor for , while the other test looked for proteins in the tumor.
Among the 99 tumor:
- 90% were
- 10% were pMMR
|
gene |
Percentage of people with a tumor that was pMMR |
|
MSH2/EPCAM |
3 % (1 of 29) |
|
0 % (0 of 26) |
|
|
11 % (2 of 18) |
|
|
46 % (6 of 13) |
Comparing and pMMR colorectal tumors
Colorectal cancers that are pMMR (and not associated with ) are typically diagnosed at advanced stages: 60% of pMMR colorectal cancers were diagnosed at a late (), while only 13% of colorectal cancers were at diagnosis.
At diagnosis, people with pMMR tumors were older (average 58 years) than those with tumors (average 43 years). The difference in tumor location within the colon (left side vs right side) was not meaningful.
Current guidelines recommend all people with colorectal cancer have a further evaluation for . Of the people in the study with pMMR tumors, 6 (of 9) met the current criteria for genetic testing for based on their personal and/or family history of cancer. Three people with with a pMMR tumor did not meet the current guidelines for genetic testing, despite having colon cancer.
What does this mean for me?
The study found that 90 percent of colorectal cancers associated with are , which is consistent with previous research. However, 10 percent of colorectal tumors among people with are pMMR and would be treated differently than a tumor.
People with due to inherited mutations in and are more likely to develop pMMR colon cancers than people with mutations in or MSH2/EPCAM. People with who had pMMR tumors were more often diagnosed at late stages.
The study emphasizes the importance of testing all colorectal tumors for MMR status, even in the setting of someone with known . The presence of can help determine treatment. For example, whether is likely to be effective or not. This study shows that individuals with can develop non-Lynch syndrome associated colorectal cancers, and therefore it is important to confirm whether a colorectal tumor is , as this may have an impact on treatment and management of at-risk family members.
Reference
Ranganathan M, Sacca, RE, et al., Prevalence and clinical implications of mismatch repair-proficient colorectal cancer in patients with . Journal of Clinical Oncology; 2023; 7:e2200675.
Disclosure: FORCE receives funding from industry sponsors, including companies that manufacture cancer drugs, tests and devices. All XRAYS articles are written independently of any sponsor and are reviewed by members of our Scientific Advisory Board prior to publication to assure scientific integrity.
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