Blood Tests and Biomarkers

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Mesothelioma blood tests are combined with X-rays, CT scans and biopsies to provide an accurate mesothelioma diagnosis. The tests find mesothelioma-specific proteins, called biomarkers, in the blood. Three mesothelioma blood tests are the MESOMARK assay, N-ERC/Mesothelin test and the Fibulin-3 test.

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Dr. Snehal Smart of Asbestos.com talks about the MESOMARK assay.
Dr. Snehal Smart of Asbestos.com talks about the MESOMARK assay.

What Are Mesothelioma Blood Tests?

Blood tests for mesothelioma identify specific substances produced by the cancer cells. These molecules are called biomarkers. They can be detected in a blood sample when a person has mesothelioma.

Examples of Mesothelioma Blood-Test Biomarkers

  • MESOMARK assay
  • N-ERC/Mesothelin Test
  • Fibulin-3 Test
  • Osteopontin
  • Megakaryocyte potentiation factor

Currently, these mesothelioma blood tests are being used in combination with imaging scans such as X-rays and CT scans to improve the accuracy and speed of cancer diagnosis.

All of these steps and tests can lead to the collection of a tissue biopsy and a pathology work up. Pathologists can closely examine cancer cells collected during surgery or biopsy.

Using sophisticated lab tests, these specialist doctors can not only differentiate mesothelioma from other tumor types, but also determine the type of mesothelioma and its genetic makeup.

Immunohistochemical markers are one example of the complex laboratory studies your pathologist may use to provide the most accurate diagnosis. This, in turn, allows your oncologists to develop the best treatment plan for your unique cancer type.

How Do Mesothelioma Blood Tests Work?

Mesothelioma blood tests work because these biomarkers tend to be produced in very small amounts or not at all by healthy cells. This means the substances normally aren’t present in a blood sample from a person without mesothelioma.

For some tumors, the proteins are unique to that specific cancer. Identifying them will indicate a person has that particular cancer.

Mesothelioma-specific biomarkers are being used as blood tests for the asbestos-related disease. They rely on the presence of proteins in the blood that only a mesothelioma tumor is likely to produce.

Other Uses for Mesothelioma Biomarkers

Mesothelioma biomarkers are being investigated for other important purposes, too. Along with helping diagnose the disease, these substances can be directly targeted to treat mesothelioma.

For example, mesothelin is a biomarker produced by mesothelioma. Ongoing clinical trials are removing patients’ immune cells, modifying them in the lab to specifically target the mesothelin on mesothelioma cells and infusing them back into the body.

Promising results from this approach were presented at the 2019 American Society of Clinical Oncology meeting. Eleven of 14 patients in the trial experienced a complete response, partial response or stable disease after an average follow up of nearly three years.

MESOMARK Assay

An assay is a test performed in a lab. The MESOMARK assay measures the quantity of SMRP (serum-measured soluble mesothelin-related peptide) in a patient’s blood sample. Abnormally high SMRP levels may indicate the presence of mesothelioma.

Some types of mesothelioma, such as sarcomatoid tumors, do not release high levels of SMRP. For this reason, the FDA recommends doctors combine the MESOMARK assay with other tests to ensure an accurate mesothelioma diagnosis.

Some insurance companies do not cover this particular blood test. However, if you have a history of asbestos exposure and therefore are at high risk for developing mesothelioma, ask your doctor if the MESOMARK assay is something you should consider.

Elevated SMRP levels identified by the MESOMARK test can help with initial mesothelioma diagnosis and sometimes are checked to monitor the cancer’s response to treatment. Declining levels may indicate the treatment is working.

Other malignant diseases, such as pancreatic cancer, ovarian cancer and primary lung cancers, may produce elevated SMRP levels. This is one drawback of the MESOMARK assay: It is not specific just to mesothelioma.

Quick Fact:

In a study of 1,086 blood samples, 99% of the healthy specimens displayed SMRP levels at or below the reference value used to indicate the presence of an asbestos-related cancer.

The MESOMARK Assay Procedure

The MESOMARK assay is completed in two steps. First, your doctor will collect a blood sample and send it to a laboratory for analysis.

Next, laboratory technicians add antibodies to the blood sample. These antibodies bind to SMRP and fragments of this protein.

Computer software analyzes the blood sample and provides a measurement of the levels of SMRP-bound antibodies. SMRP levels at or above a certain reference point may suggest the presence of mesothelioma or another malignant pleural disease.

Elevated Serum SMRP levels bar graph
Percent of patients who had elevated serum SMRP levels

The MESOMARK blood test may someday serve as a screening tool for patients at high risk for mesothelioma who don’t yet have the disease.

Currently, it is only used in diagnosing suspected cases of mesothelioma, although a 2019 meta-analysis identified mesothelin blood levels as significantly lower in all control groups compared with people who have malignant pleural mesothelioma.

This suggests mesothelin may be a good candidate for a screening biomarker in people at high risk of developing mesothelioma.

Quick Fact:

In one study of 40 subjects with a history of asbestos exposure, seven individuals displayed elevated SMRP levels. Within five years of the blood test, three of these patients were diagnosed with the disease. None of the 33 patients with normal SMRP levels developed mesothelioma in the next eight years.

N-ERC/Mesothelin Test

The N-ERC/Mesothelin test detects a specific form of mesothelin known as N-ERC/mesothelin.

The test is similar to MESOMARK, but it uses a specially designed enzyme to find a particular version of the mesothelin molecule. This increases the test’s accuracy.

The N-ERC/mesothelin test is 95% effective at detecting mesothelioma. However, it is only 76% effective at ruling mesothelioma out because mesothelin is produced by a few other types of cancer, too.

Even though it is more accurate than MESOMARK, the N-ERC/Mesothelin blood test cannot serve as a single test to diagnose mesothelioma.

Fibulin-3 Test

Fibulin-3 is a protein produced by mesothelioma cells. It can be detected in pleural fluid and blood. Mesothelioma specialist Dr. Harvey Pass helped develop and validate the fibulin-3 test for mesothelioma diagnosis.

In 2012, he co-authored a study demonstrating fibulin-3 is 96.7% effective at detecting mesothelioma and 95.5% effective for ruling it out in people without the disease.

Other studies have found the test less effective for detecting mesothelioma, depending on when and how it is used. For example, when used on blood samples previously collected from mesothelioma patients, it was not as accurate.

A 2019 meta-analysis found significantly higher fibulin-3 blood levels in people with mesothelioma compared with all non-mesothelioma control groups, making it a potentially effective blood test biomarker in people at high risk of developing mesothelioma.

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Other Biomarker-Based Blood Tests

Other mesothelioma biomarker tests determine levels of osteopontin and megakaryocyte potentiation factor (MPF) in blood samples.

Researchers have demonstrated mesothelioma patients have higher concentrations of these biomarkers compared with healthy individuals or patients with other cancers.

Osteopontin and MPF blood tests are not dependable or accurate enough to make a definitive mesothelioma diagnosis, but they can play a significant role in monitoring the disease once a diagnosis is confirmed with X-rays, CT scans and tissue biopsies.

Human Osteopontin ELISA Kit from R–D Systems

Osteopontin levels are elevated in mesothelioma patients — even when compared to patients with benign asbestos-related conditions such as asbestosis and pleural thickening.

This means the human osteopontin ELISA kit is a reliable biomarker test for differentiating between healthy asbestos-exposed individuals and those who have developed mesothelioma.

Other diseases can elevate osteopontin levels too, including cancers of the lung, colon and breast and tuberculosis, and osteopontin cannot differentiate malignant mesothelioma and these conditions.

It can be useful for screening asbestos-exposed populations, monitoring treatment and predicting prognosis for mesothelioma patients.

Human Megakaryocyte Potentiation Factor (MPF) ELISA Kit

Blood tests can identify the presence of a biomarker called megakaryocyte potentiation factor (MPF). Doctors do not fully understand the biological function of MPF, but they know it is released into the bloodstream of mesothelioma patients in extremely high quantities.

In one small study, laboratory technicians identified MPF in blood samples from 91% of late-stage patients. They did not detect MPF in the blood of healthy donors, although ovarian cancer and pancreatic cancer also can lead to elevated MPF blood levels.

While the MPF biomarker test alone cannot provide an accurate diagnosis, levels may decrease after effective mesothelioma treatments such as successful surgical debulking.

This indicates that MPF blood testing can help monitor a patient’s response to surgery.

Other Blood Test Biomarkers

When asbestos fibers enter the body, damage begins to occur. Doctors can monitor the byproducts of asbestos-related cell to potentially track the progression of asbestos-related disease.

8OHdG

8OHdG is a biomarker indicating cell damage due to oxidation. This biomarker may be present in blood samples during the early stages of cancer development. Elevated 8OHdG levels can occur in people occupationally exposed to asbestos and have been linked to asbestosis.

This biomarker is produced by many cancers, not just mesothelioma. Additionally, exposure to cigarette smoke and heavy metals can create 8OHdG.

However, higher 8OHdG levels correlate with more severe asbestosis. One study found the combination of 8OHdG and the biomarkers VEGFbeta and SMRPs is effective for identifying people with varying degrees of asbestos exposure.

Estrogen Receptor-β

While ER-β is not used to diagnose mesothelioma, it may be useful for prognosis and treatment decisions. A 2014 study found higher levels of activated ER-β in pleural mesothelioma cells improved response to cisplatin chemotherapy.

Epidermal Growth Factor Receptor (EGFR)

Like ER-β, EGFR is activated by asbestos exposure and may play a role in the development of mesothelioma. Because EGFR is produced by a variety of cancers, it cannot be used to diagnose mesothelioma. However, it may be useful for monitoring treatment response.

Calretinin

A 2017 study published in the journal BMC Cancer detailed the possible use of the blood biomarker calretinin to improve mesothelioma diagnosis.

The team of Australian and German researchers developed a test to detect calretinin in blood samples and found it performed similarly to mesothelin. Calretinin appears most likely to improve diagnosis epithelioid and biphasic disease, but not sarcomatoid cell mesothelioma.

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Registered Nurse and Patient Advocate

Karen Selby joined Asbestos.com in 2009. She is a registered nurse with a background in oncology and thoracic surgery and was the regional director of a tissue bank before becoming a Patient Advocate at The Mesothelioma Center. Karen has assisted surgeons with thoracic surgeries such as lung resections, lung transplants, pneumonectomies, pleurectomies and wedge resections. She is also a member of the Academy of Oncology Nurse & Patient Navigators.

Walter Pacheco, Managing Editor at Asbestos.com
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Last Modified July 29, 2019

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