Written by Karen Selby, RN | Medically Reviewed By Dr. Jeffrey Velotta | Edited By Walter Pacheco | Last Update: November 20, 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. They help 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. [It may] contribute to an earlier, non-invasive diagnosis of MM.

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 promotes 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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Using Calretinin to Diagnose Mesothelioma

Calretinin is a protein. Researchers make calretinin antibodies to detect mesothelioma. Doctors use the protein to tell the difference between epithelioid and biphasic mesothelioma. These are the two most common cell types of this cancer. The protein also helps distinguish mesothelioma from adenocarcinoma.

Pathologists stain a cancer tissue sample with a calretinin antibody. It 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 study found calretinin had a high success rate of detecting mesothelioma. An exception was 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, doctors diagnose most mesothelioma cases after tumors spread and symptoms arise.

Snehal Smart, M.D. and Patient Advocate at The Mesothelioma Center

Calretinin helps the pathologist distinguish between epithelial mesothelioma and adenocarcinoma. This reduces the chances of misdiagnosis.

Differentiating Mesothelioma from Other Cancers

Calretinin immunostain from pleural mesothelioma
Calretinin stains viewed through a microscope.

Calretinin was the first biomarker to differentiate epithelioid and biphasic mesothelioma from adenocarcinoma. The latter is the most common type of cancer in the lungs, prostate, esophagus and colon.

Calretinin stains differ between mesothelial and adenocarcinoma cells. Because of this, calretinin plays a vital role in preventing mesothelioma misdiagnosis.

Doctors can misdiagnose desmoid fibromatosis as mesothelioma based on calretinin positivity. A 2022 study in the World Journal of Surgical Oncology reported this data.

Calretinin as a Potential Target for Mesothelioma Treatment

Doctors have not used calretinin to treat mesothelioma. Researchers suspect it might have clinical value. Doctors are exploring the use of calretinin to track tumor response to treatment.

Quick Fact
Calretinin, MALAT1 and GAS5 may predict tumor recurrence after mesothelioma surgery. A 2024 German study reported this among surgical patients.
Source: Lung Cancer

In a 2013 study, researchers explored calretinin’s functions in mesothelioma development. In mice, they found that a lack of calretinin caused cancer cells to die within 72 hours. These promising results make calretinin a potential target for mesothelioma gene therapy.

A drug targeting CALB2 — the gene that encodes calretinin — could treat mesothelioma. Another approach would be a drug that downregulates calretinin itself. The authors said that blocking the biomarker could help control mesothelioma.

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