Blood Test

Mesothelioma Blood Test

One of the difficulties in diagnosing pleural mesothelioma is distinguishing it from adenocarcinoma of the lung. A new testing method being developed that has proven more successful in helping pathologists make this differentiation between the two types of lung disease is looking for the presence of biomarkers in the patient’s blood.

What is a Biomarker?

The term “biomarker” refers to the measurement of the level of certain proteins in the blood whose presence indicates that the patient has a particular disease. Biomarkers can also be measure to determine how severe the disease may be.

What Biomarkers are Indications that a Patient has Mesothelioma?

There are two biomarkers that clinical research has shown to be effective in determining the presence of mesothelioma. The first is called mesothelin. This protein is normally found on the surface of the mesothelial cells that make up the lining of the pleura. However, when a patient has mesothelioma, the protein is overexpressed, meaning there is more of it than there should be.

What are actually measured are soluble mesothelin-related peptides (SMRPs), which are thought to be either fragments that have broken off the mesothelin, or abnormal versions of mesothelin that can no longer bind to the mesothelial cells because they have been altered and are now free floating. While SMRPs are specific to mesothelioma, they are not always accurate indicators that the disease is present, or what is known as sensitivity.

Research Suggests a Possible Explanation for the SMRPs Lack of Sensitivity

In a study titled “The Relationship between Tumor MSLN Methylation and Serum Mesothelin (SMRP) in Mesothelioma”, published online August 1, 2011in Epigenetics, researchers may have uncovered the reason why SMRPs are not effective as biomarkers.

The objective of their study was to determine whether or not epigenetic change of the MSLN gene in a tumor was the reason for the poor sensitivity of SMRP. An epigenetic change is a modification in the expression of the gene that has been caused by something other than a modification in the DNA sequence which contains the gene.

What these scientists discovered was that inhibiting of a process called methylation was at the root of the problem, Methylation adds a group of alkyls called methyls to a certain location of the DNA sequence called a CpG site. They found three possible CpG regions where methylation was inhibited in the tumor MSLN gene promoter, which is where the development of the gene begins.

Here’s what else they found:

• Methylation in the MSLN gene promoter was much higher in normal pleural tissue than in tumor tissue.
• Methylation in the MSLN gene was much higher in mesothelioma patients that tested negative for SMRPs than in those that tested positive for them.
• A certain group of tumors kept the methylation that should have been lost

What this means is that the normal methylation that happens in pleural tissue is lost in most tumors, but not necessarily all of them. If the tumor has retained the methylation, the patient will test negative for SMRPs and the results are interpreted as the patient does not have mesothelioma.

Osteopontin is the Other Biomarker Used to Diagnose Mesothelioma

This protein is overexpressed in several types of cancer including mesothelioma. In a study titled Combined Serum Mesothelin and Plasma Osteopontin Measurements in Malignant Pleural Mesothelioma, published online June 2, 2011 in the Journal of Thoracic Oncology, the researchers tested:

• 93 healthy individuals
• 111 patients with benign respiratory disease
• 31 patients with pleural mesothelioma

SMRPs and plasma levels of osteopontin were determined using commercially available assay kits that are designed for this type of measurement.

The researchers found that both the individual SMRP levels and osteopontin levels were significantly higher for mesothelioma patients than for the other two groups. In addition, when they combined the two markers, they were even more accurate in diagnosing the mesothelioma.