Proteins are essential building blocks for your body’s cells. Different organs and tissues in your body are made of different types of proteins. These proteins give doctors critical clues when trying to diagnose cancer.

To choose suitable treatment options, doctors must know where the cancer originated. This is often challenging because cancer usually spreads into various types of tissue by the time a patient has symptoms.

For example, when doctors find cancer in the lung tissue and the membrane (mesothelium) next to it, they need to determine whether it is lung cancer, mesothelioma or cancer originating somewhere else in the body.

Immunohistochemical tumor markers help doctors determine what kind of cancer is present.

What Is Immunohistochemistry?

Immunohistochemistry is one of the techniques pathologists use when they examine samples of cancer tissue. This technique uses antibodies to make specific proteins in cells visible under a microscope.

Immunohistochemical Markers: Immunohistochemical tumor markers are proteins that help doctors tell the difference between different types of cancer. A composite image taken under a microscope shows cells of various types stained in different colors to highlight differences in cancer diagnosis.

An antibody is a molecule that binds to another type of molecule. Pathologists use antibodies designed to stain specific proteins in a color that is easy to see.

If a pathologist suspects mesothelioma, they will use antibodies to look for proteins that usually occur in mesothelioma cells. These proteins are positive cancerous mesothelioma markers.

The pathologist will also apply other antibodies to double-check for proteins that usually do not occur in mesothelioma cells. These other proteins are positive markers for different types of cancer, but they are not markers for mesothelioma.

After staining the cancer tissue sample with the antibodies, the pathologist looks at it through a microscope to see which antibodies stuck to the cells and which did not.

If the pathologist can see many positive markers but few markers for other cancers, then the analysis points to mesothelioma.

However, immunohistochemistry is only one part of diagnosing mesothelioma. Pathologists also have to pay attention to the tumor’s pattern of formation and other features of the cancer cells.

Common Mesothelioma Markers

The International Mesothelioma Interest Group identified calretinin, cytokeratin 5/6, WT-1 protein, podoplanin and mesothelin as some of the most helpful markers.

A 2021 research study suggests that more recently discovered markers, MUC4 and GATA 3, could aid doctors in the distinction between pleural sarcomatoid mesothelioma and pulmonary sarcomatoid carcinoma.

Immunohistochemistry for mesothelioma is still developing as a science, and different pathologists have experience with using different antibodies. Because of this, there is no standard set of markers for mesothelioma.


Calretinin is a calcium-binding protein that occurs in various types of cells in the body. It is found in almost all mesothelioma cases and sometimes occurs in other types of cancer. It is beneficial for diagnosing sarcomatoid mesothelioma.

Cytokeratin 5 and 5/6

Cytokeratins are proteins that provide cells with structural support. Different parts of the body use different types of cytokeratins. Cytokeratins are numbered based on where they are found in the body.

Cytokeratin 5 or 5/6 is found in more than three-fourths of pleural mesothelioma cases, but it is also found in certain types of lung cancer. It is not as helpful in diagnosing peritoneal mesothelioma. It also may not be valid for diagnosing sarcomatoid mesothelioma.

WT-1 Protein

The WT-1 protein helps certain types of cells grow and mature by regulating the activity of genes. Most pleural mesothelioma cases are positive for WT-1, while most lung cancer cases are negative. WT-1 is not as helpful in diagnosing peritoneal mesothelioma or sarcomatoid mesothelioma.

Podoplanin (D2-40)

Through tissue staining, pathologists use podoplanin, a protein, to tell the difference between epithelioid mesothelioma and adenocarcinoma — a type of cancer that forms in the mucus-secreting membranes throughout the body.

While the specific function of this protein has yet to be determined, it has proven helpful as a diagnostic marker for several cancers. It is highly expressed in squamous cell carcinomas, malignant mesothelioma and brain tumors.


Mesothelin is a protein found on the surface of mesothelial cells and certain types of cancer cells. Mesothelin is found in all mesothelioma cells, so it helps rule out certain mesothelin-negative cancers, such as kidney cancer that has spread to the lungs.

Markers for Other Types of Cancer

It is impossible to rule out other types of cancer using only positive mesothelioma markers. Pathologists must also test for immunohistochemical tumor markers that rarely occur in mesothelioma.

Common Negative Mesothelioma Markers

  • B72.3
  • CD15
  • CDX2
  • CEA
  • MOC31
  • Naspin A
  • PAX2
  • PAX8
  • TTF-1

If negative mesothelioma markers appear, the tumor may be a different type of cancer.