Written by Karen Selby, RN | Medically Reviewed By Dr. Raja Michael Flores | Edited By Walter Pacheco | Last Update: November 14, 2024

The Role of Tumor Markers in Cancer Diagnosis

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.

Doctors need to know the cancer’s origin to pick the right treatment. This can be tough because cancer spreads to different tissues before symptoms appear.

For example, when doctors find cancer in the lung and the nearby membrane (mesothelium), they must determine its type. It could be lung cancer, mesothelioma, or cancer from elsewhere in the body.

Immunohistochemical tumor markers help doctors find out what cancer is present.

What Is Immunohistochemistry?

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.

Immunohistochemistry is a method pathologists use to study mesothelioma cancer tissue samples. It employs antibodies to make certain proteins in cells visible under a microscope.

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 check for specific proteins. These proteins are typically in mesothelioma cells and indicate cancer.

The pathologist will also use other antibodies to check for proteins not typically found in mesothelioma cells. These proteins are markers for other cancers but not for mesothelioma.

After staining the cancer tissue sample with the antibodies, the pathologist looks at it through a microscope. They look for which antibodies stuck to the cells and which did not. If the pathologist finds many positive markers but few for other cancers, it suggests mesothelioma.

Immunohistochemistry is just one step in diagnosing mesothelioma. Pathologists also need to look at the tumor’s pattern and the cancer cells’ characteristics.

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 study suggests that newly found markers may help doctors distinguish between pleural sarcomatoid mesothelioma and pulmonary sarcomatoid carcinoma. These markers are MUC4 and GATA 3.

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

Calretinin

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 give cells support. Different body parts use various types. They’re numbered by their locations in the body. Cytokeratin 5 or 5/6 is found in over 75% of pleural mesothelioma cases. However, it is also present in some lung cancers. Its value in diagnosing peritoneal mesothelioma is limited. Similarly, it may not be reliable for sarcomatoid mesothelioma.

WT-1 Protein

The WT-1 protein regulates genes to help some cells grow and mature. Most pleural mesothelioma cases have WT-1, while most lung cancer cases do not. WT-1 is not very useful for diagnosing peritoneal or sarcomatoid mesothelioma.

Podoplanin (D2-40)

Pathologists use a tissue stain for podoplanin. It helps to tell apart epithelioid mesothelioma and adenocarcinoma, a cancer in mucus-secreting membranes.

The exact function of this protein is still unknown. Yet, it is a helpful marker for several cancers. Notably, it is highly present in squamous cell carcinomas, mesothelioma and brain tumors.

Mesothelin

Mesothelin is a protein on the surface of mesothelial and some cancer cells. It’s found in all mesothelioma cells. Therefore, it helps rule out certain cancers, such as kidney cancer that has spread to the lungs.

Markers for Other Types of Cancer

You can’t rule out other cancers with just positive mesothelioma markers. Pathologists need to check for rare immunohistochemical tumor markers as well.

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.

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