Mesothelioma testing is rarely simple or straightforward, and many patients undergo multiple diagnostic tests to confirm or rule out cancer. While imaging and biopsies remain essential, biomarkers and blood tests for many cancer types are gaining interest, including mesothelioma.[1] Research continues to improve the technique of using biomarkers to aid in detecting the presence of cancer.
What Tests Are Done to Diagnose Mesothelioma?
Mesothelioma testing is complicated and varies depending on the patient. There is no single test that can diagnose this rare cancer. Doctors use a variety of tests to determine if a patient has mesothelioma:
- Physical exam and symptom review
- Imaging scans, including X-rays, CT, MRI, and PET scans
- Biopsies to examine the cells under a microscope
- Blood tests for characteristic biomarkers
What Are Biomarkers?
A biomarker is a molecule of biological origin found in tissues, blood, or other bodily fluids. They are characteristic of some process or disease.[2] Biomarkers are not necessarily bad. For example, certain hormones in urine are biomarkers indicating pregnancy. Biomarkers are also useful in diagnosing diseases, including cancer.
Pathologists can find various types of biomarkers in the blood to indicate cancer in the body. These include proteins, nucleic acids like DNA and RNA, antibodies, and others.
If there is a biomarker cancer cells are known to produce, its presence in the blood can be part of an overall diagnosis. Some biomarkers are general to all types of cancers. Others may indicate a specific type.[3]
Currently, no approved biomarker is used for mesothelioma screening purposes. Doctors still use blood tests to look for biomarkers because they add to the diagnostic picture. No single biomarker always indicates mesothelioma, but certain patterns help distinguish it from other types of cancer.
Is There a Blood Test for Asbestos Exposure?
There is no asbestos blood test. To find asbestos fibers in the body requires a biopsied tissue sample. Doctors don’t usually directly test for asbestos, as exposure usually occurred decades earlier. Instead, they look for a response to that exposure: symptoms, pleural plaques or thickening, tumors, inflammation, and scarring.
Mesothelioma Tests for Biomarkers
Doctors use a wide range of biomarkers when diagnosing mesothelioma. No biomarker is a perfect indicator, but together with other diagnostic tests, they help confirm the diagnosis.
Mesothelin
One of the most specific biomarkers for mesothelioma is soluble mesothelin-related protein (SMRP). These proteins are produced and released by cancer cells of the mesothelium.
SMRP is normal in mesothelium cells but often overproduced in cancerous cells. The MESOMARK assay is a blood test that measures SMRP levels.[4]
Studies indicate the MESOMARK assay can be a useful diagnostic tool for mesothelioma. Compared to healthy people, most patients with mesothelioma have elevated levels of SMRPs.
Unfortunately, this test is not perfect. Some patients with mesothelioma do not have elevated levels. In addition to diagnosing cancer, MESOMARK can also be used to track the progress of mesothelioma. In patients with mesothelioma, levels of SMRP usually go up as the condition worsens.[5]
There is potential for SMRP as a biomarker to act as an early test for mesothelioma. People exposed to asbestos could be screened using the assay to detect rising levels of SMRP early, allowing earlier diagnosis and better treatment options.[6] More research is needed before it’s used for screening purposes.
Another test used to detect mesothelin proteins is the N-ERC/mesothelin test. This test is similar to the MESOMARK assay but can be more accurate thanks to a special enzyme to detect the proteins. It also can be used for other cancers, such as pancreatic and ovarian cancers. While this newer test is more accurate, it is still not a definitive biomarker test.[7]
Fibulin-3
Another biomarker for mesothelioma is the protein fibulin-3. Like SMRP, this protein is released in larger quantities in mesothelioma cancer cells. The protein can be found in blood and pleural fluid.
One early study using fibulin-3 as a biomarker found it was 95% effective at ruling out mesothelioma, and the test was more than 96% more effective at detecting it. Additional research is needed before it can be used for mesothelioma screening.[8]
Osteopontin
Osteopontin is another protein typically found at higher levels in the blood of patients with mesothelioma. There are, however, other types of cancer that also elevate blood levels of this bone-related protein. These include lung cancer, breast cancer, and colon cancer.
Tests for osteopontin may be most useful in screening people with known asbestos exposure. There is a strong connection between the levels of this biomarker and the extent of asbestos exposure. It may be useful in determining how much asbestos a person was exposed to and, therefore, the level of risk for developing mesothelioma.[9]
Megakaryocyte Potentiating Factor (MPF)
Another potentially useful biomarker is megakaryocyte potentiating factor (MPF), a protein made by a precursor of mesothelin.
No one yet understands what MPF does in the body; however, it has been detected at elevated levels in people known to have mesothelioma. Other types of cancer may cause elevated levels of MPF, like ovarian and pancreatic cancer.
One study found levels of MPF changed before and after tumor removal surgery. The amount of MPF in the blood varied depending on how much of the tumor could be removed. This means it could be a useful test for determining how much cancerous tissue remains after surgery.[10]
Other Mesothelioma Biomarkers
There are a few other biomarkers that doctors sometimes use but that are less important and informative in diagnosing mesothelioma:[11][12]
- 8-oxo-dGuo/8-OHdG. These biomarkers are signs of oxidative stress in DNA. They signal that DNA has been damaged by something, like asbestos, but are not specific to mesothelioma.
- Epidermal Growth Factor Receptor. EGFR similarly lacks specificity, but it is also known to play a role in how mesothelioma develops.
- Estrogen Receptor-β. While this marker isn’t very useful for diagnosing mesothelioma, it can help develop a prognosis. It indicates how a patient might respond to standard chemotherapy.
- Interleukin-6/VEGF. Mesothelioma cells excrete interleukin-6, a marker of inflammation and immune response. Interleukin-6, in turn, produces vascular endothelial growth factor. Researchers are targeting these markers for treatments.
- Calretinin. Calretinin is a protein that has been useful in identifying epithelial and biphasic, but not sarcomatoid mesothelioma.
The Latest in Mesothelioma Biomarker Research
No biomarker is yet a perfect diagnostic factor for mesothelioma. Researchers continue to investigate compounds to improve diagnoses with some potential biomarkers currently under investigation:
- High Mobility Group Box 1 Protein. HMGB1 is a protein researchers believe may be diagnostic for mesothelioma. Mesothelioma cells release the protein as they die, triggering an inflammatory response. Studies indicate that a certain form of the HMGB1 could differentiate between healthy asbestos-exposed individuals and those with mesothelioma.[13]
- Claudins. This group of proteins is produced in epithelial cells. Researchers have found that claudin-15 is specifically expressed in mesothelial cells. They found the protein in mesothelioma tissue but not in the tissue of other cancers. This protein may help distinguish between mesothelioma and other cancer types.[14]
Tracking Biomarkers in At-Risk Patients
Blood tests for biomarkers have the potential to detect mesothelioma in patients; however, there are limitations. Research continues as scientists seek more accurate tests to diagnose mesothelioma specifically.
In the meantime, these biomarker blood tests can help monitor mesothelioma risk in select cases of people exposed to asbestos.
Blood tests for biomarkers will hopefully have a role in routine use in the future. They are still not accurate enough to be utilized for widespread early detection of cancer. The most important thing is to discuss risk factors with your medical care team, and they can help determine the most appropriate screening protocols.
