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Calretinin
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Calretinin is a calcium-binding protein originally found in neurons. It is also overexpressed in most types of malignant mesothelioma. Pathologists use calretinin as a selective marker to diagnose mesothelioma, and researchers are testing the protein as a target for cancer therapy.
Written by Karen Selby, RN | Medically Reviewed By Dr. Jeffrey Velotta | Edited By Walter Pacheco | Last Update: August 8, 2024
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Written by Karen Selby, RN | Medically Reviewed By Dr. Jeffrey Velotta | Edited By Walter Pacheco | Last Update: August 8, 2024
What Is Calretinin?
Calretinin is a protein involved in calcium signaling. It has become a valuable biomarker for specific illnesses. These include Hirschsprung disease and malignant mesothelioma.
Pathologists use biomarkers in immunohistochemistry to tell different forms of cancer and cell types apart. Calretinin is one of several immunohistochemical markers used to diagnose malignant mesothelioma.
Calretinin is a useful biomarker that can distinguish MM from other asbestos-related diseases and could, therefore, contribute to an earlier non-invasive diagnosis of MM.
Dr. Cita Zupanc, et al, medical director of the Military Medical Unit, Slovenian Army
A 2017 study showed calretinin helps detect most major subtypes of malignant mesothelioma. The study also discussed calretinin as a target for a new treatment approach. An earlier study in the International Journal of Cancer showed calretinin plays a role in mesothelioma cell growth.
Certain neurons in the nervous system express calretinin. It is also found in specialized cells, such as Leydig cells. These cells produce testosterone. The calretinin protein is present in several other locations, including hair follicles.
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Calretinin is a protein. Antibodies are made against the protein to detect malignant mesothelioma. Doctors use the protein to tell the difference between epithelioid and biphasic mesothelioma — the two most common cell types of this cancer. The protein also helps distinguish mesothelioma from adenocarcinoma.
Pathologists do this by staining a cancer tissue sample with a calretinin antibody that reacts to calretinin. A calretinin stain tests positive in most cases of mesothelioma.
55% and 90%
The percentage of calretinin detection in sarcomatoid and epithelial mesothelioma patients, respectively.
Like many other biomarkers, calretinin is not helpful in detecting sarcomatoid cells. Sarcomatoid mesothelioma is the rarest cell type and the most difficult to treat. A smaller percentage of sarcomatoid cases test positive for calretinin than epithelial cases. Pathologists may test for podoplanin, another immunohistochemical marker when sarcomatoid mesothelioma is suspected.
A 2017 BMC Cancer study found calretinin had a high success rate of detecting mesothelioma, except in sarcomatoid cases. The study included 199 cases of pleural mesothelioma in Australia and Germany. It compared calretinin to mesothelin, an established biomarker in all mesothelioma cells. Calretinin’s performance was comparable with mesothelin. Combining both markers increased diagnostic sensitivity from 66% to 75%.
Researchers hope combining calretinin and mesothelin with other biomarkers will one day make the early detection of malignant mesothelioma possible. Currently, most mesothelioma cases are diagnosed after tumors spread, and symptoms arise. “That would be a major step toward the application of biomarkers in medical surveillance programs of workers with former exposure to asbestos,” the study’s authors concluded.
Calretinin positivity on a tissue biopsy helps the pathologist distinguish between epithelial mesothelioma and adenocarcinoma, thereby reducing the chances of a misdiagnosis.
Differentiating Mesothelioma from Other Cancers
Calretinin stains viewed through a microscope.
Calretinin was the first biomarker to differentiate epithelioid and biphasic mesothelioma from adenocarcinoma. Adenocarcinoma is the most common type of cancer in the lungs, prostate, esophagus and colon.
There is a statistically significant difference in the staining pattern of calretinin between mesothelial cells and adenocarcinoma cells. Because of this, calretinin plays a vital role in preventing mesothelioma misdiagnosis.
A 2022 study in the World Journal of Surgical Oncology claimed that there are case reports of desmoid fibromatosis diagnosed initially as malignant mesothelioma based on calretinin positivity.
Calretinin as a Potential Target for Mesothelioma Treatment
While calretinin has not been used yet to treat mesothelioma, researchers suspect it might have clinical value. Until the therapeutic use of calretinin is further developed, doctors are investigating its potential to track mesothelioma tumor response to treatment.
Quick Fact
Calretinin, MALAT1 and GAS5 may predict tumor recurrence after mesothelioma surgery, according to a 2024 German study.
Source:
Lung Cancer
In a 2013 study, researchers explored calretinin’s functions in tumor development. They found the depletion of calretinin in mice models led to mesothelioma cell death within 72 hours and blocked cell growth. These promising results make calretinin a potential target for mesothelioma gene therapy.
A drug targeting CALB2 — the gene that encodes calretinin — could potentially treat mesothelioma. Another approach would be a drug that downregulates calretinin itself.
“These results demonstrate that downregulation of CR [calretinin] had a strong effect on the viability of MM [malignant mesothelioma] cells,” the authors of the study wrote.
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