Pathologists use immunohistochemistry to tell apart different forms of cancer and different cancer cell types. Calretinin is one of several immunohistochemical markers used to diagnose malignant mesothelioma.

A 2017 study in BMC Cancer showed calretinin is useful for detecting all major subtypes of malignant mesothelioma except the sarcomatoid cell type. That study also discussed calretinin as a possible target for a new treatment approach.

A 2013 study in the International Journal of Cancer had already shown calretinin is essential for mesothelioma cell growth and survival.

What Is Calretinin?

Calretinin is a binding protein involved in calcium signaling. It is encoded by the CALB2 gene and plays an essential role in how cells work.

Calretinin is naturally expressed in certain neurons in the nervous system. It is also found in specialized cells such as Leydig cells, which produce testosterone in men.

The protein is expressed in several other locations, including hair follicles. Calretinin has become a useful biomarker for illnesses such as Hirschsprung disease and malignant mesothelioma.

Using Calretinin to Diagnose Mesothelioma

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 the 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.

Like many other biomarkers, calretinin is not useful for detecting sarcomatoid cells. Sarcomatoid mesothelioma is the rarest cell type and the most difficult to treat. Only about 31 percent of sarcomatoid cases test positive for calrentinin.

Pathologists may test for podoplanin, another immunohistochemical marker, when sarcomatoid mesothelioma is suspected.

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. In the 2017 BMC Cancer study, 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 found in all mesothelioma cells. Calretinin’s performance was comparable with mesothelin. Combining both markers increased diagnostic sensitivity from 66 to 75 percent.

Researchers hope combining calretinin and mesothelin with other biomarkers will one day make the early detection of malignant mesothelioma possible. Currently, most cases of mesothelioma 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 authors of the study concluded.

Differentiating Mesothelioma from Other Cancers

Calretinin was the first biomarker to differentiate epithelioid and biphasic mesothelioma from adenocarcinoma. Adenocarcinoma is the most common type of cancer that forms 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 an important role in preventing mesothelioma misdiagnosis.

Calretinin as a Potential Target for Mesothelioma Treatment

In the 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.

“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.

A drug targeting CALB2 — the gene that encodes calretinin — could potentially treat mesothelioma. Another approach would be a drug that downregulates calretinin itself.

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