Every part of fighting mesothelioma, from diagnosing this cancer to treating it, is a challenge. Everyone involved in the battle faces difficulties.
Medical experts are regularly trying to make this fight easier. One of the strongest allies — and one that could play a more significant role in the future — is immunohistochemistry.
A new medical article published in Translational Lung Cancer Research details how immunohistochemistry can help diagnose and manage malignant mesothelioma. Researchers from the pathology departments at Brigham and Women’s Hospital (Boston, Massachusetts) and the University of Chicago laid out the evidence supporting this diagnostic practice.
With the help of using antibodies to stain tissue or fluid samples, pathologists can better-identify mesothelioma. They may even be able to utilize therapies to target the proteins revealed during staining — thus possibly improving survival.
How Is Immunohistochemistry Used for Diagnosing Mesothelioma?
Immunohistochemistry is a pathology process used to uncover the presence of cancerous proteins. Pathologists use “stains” on tissue samples to create an interaction with these proteins, which reveals the cancer. The stains are made up of antibodies, which are proteins that the immune system uses to fight against viruses and diseases.
The most common positive stains for diseased mesothelial cells, which comprises mesothelioma, involve using or targeting these proteins:
- Broad-spectrum cytokeratin
- Cytokeratin 5/6
- Podoplanin (D2-40)
Pathologists start by examining the tissue samples under a microscope. In some cases, they can tell that mesothelioma exists through inspection. However, getting reassurance from antibody staining will validate their beliefs.
Pathologists often start with the six antibodies listed above. Broad-spectrum cytokeratin, for instance, is exceptionally reliable. The researchers from Brigham and Women’s Hospital and the University of Chicago wrote that this stain:
- Reveals the presence of epithelioid mesothelioma close to every time
- Shows sarcomatoid mesothelioma approximately 90% of the time
Calretinin is another reliable stain. The researchers found that it has between 80% and 100% sensitivity for epithelioid mesothelioma cells. It detects sarcomatoid mesothelioma cells between 50% and 60% of the time.
The other four stains are also reliable for diagnosing mesothelioma, according to the combined research of Brigham and Women’s Hospital and the University of Chicago:
- Cytokeratin 5/6 — Reveals mesothelioma between 51% and 100% of the time for epithelioid cases
- WT-1 — Successfully identifies epithelioid mesothelioma cells between 70% and 100% of the time
- Podoplanin (D2-40) — Shows epithelioid mesothelioma cells between 80% and 100% of the time, and reveals sarcomatoid mesothelioma cells between 75% and 90% of the time
- HEG1 — Shows a positive stain between 91% and 99% of epithelioid cases, and between 64% and 78% of sarcomatoid cases
Another challenge exists, though, for pathologists. These stains aren’t reliable for detecting only mesothelioma, which partly explains why misdiagnosis happens so often.
Why Immunohistochemistry Is Essential for Diagnosing Mesothelioma
Immunohistochemistry has become an integral step in diagnosing mesothelioma. The rarity of this disease creates issues in accurately diagnosing it.
There are between 2,500 and 3,000 new mesothelioma cases each year in the United States. That number is on the low end of annual instances for a type of cancer. This leads to limited opportunities for pathologists to examine the disease — and to get comfortable identifying it under microscopic examination.
The two main types of mesothelioma — pleural mesothelioma and peritoneal mesothelioma — are often confused with more common cancers, such as lung cancer and ovarian cancer. Treatment options and prognosis for mesothelioma differs from other cancers, so an accurate diagnosis is crucial.
The stains used for mesothelioma immunohistochemistry can help avoid this confusion. The researchers from the two hospitals showed how each stain reveals positive markers for other types of cancer.
Mesothelioma pathologists can use each stain in a “process of elimination” to rule out potential other diagnoses. For instance, WT-1 is nonexistent in lung cancer but is nearly 100% reliable for identifying ovarian cancer. Calretinin and cytokeratin 5/6 are far less dependable for identifying ovarian cancer but more reliable for detecting specific types of lung cancer.
Pathologists are encouraged to use multiple staining methods to ensure an accurate diagnosis. This deliberate scrutiny is why staining, in combination with microscopic examination, is beneficial.
How Immunohistochemistry Can Improve Mesothelioma Treatment
Immunohistochemistry can improve mesothelioma treatment in numerous ways. The two main cell types — epithelioid and sarcomatoid — have varying prognoses and require different treatment approaches. Epithelioid is often associated with longer survival times and more aggressive therapies, such as surgery.
Due to the rarity of this disease, some pathologists have difficulty distinguishing between the two and may misdiagnose a patient.
“In challenging cases, a cytokeratin immunostain may assist in distinguishing sarcomatoid and epithelioid patterns by highlighting greater cell-cell cohesion in the latter,” the researchers wrote.
Immunohistochemistry can also indicate whether a treatment may work. Immunotherapy, in particular, may benefit from extensive staining.
Immunotherapy involves helping the body’s immune system naturally fight diseases. Frequently, the proteins in mesothelioma suppress the immune system. Many types of immunotherapy, such as anti-PD-L1 drugs, target these proteins.
PD-L1 is a protein often expressed in mesothelioma cells. Drugs such as pembrolizumab (brand name Keytruda) block these proteins from interacting with and subduing the immune system’s T-cells. Therefore, staining for PD-L1 could reveal whether immunotherapy can help a patient.
This type of thought process could evolve mesothelioma treatment. Targeted therapy specialized for each patient is an emerging approach to fighting mesothelioma, and immunohistochemistry could be a cornerstone of this new mentality.
Sources & Author
- Application of immunohistochemistry in diagnosis and management of malignant mesothelioma. Translational Lung Cancer Research. Retrieved from:
http://tlcr.amegroups.com/article/view/34675/24350. Accessed: 06/02/2020.
Sources & Author