Loss of the BAP1 protein and high levels of the EZH2 protein are two very specific characteristics of malignant mesothelioma and may serve as biomarkers to help researchers differentiate the disease from benign growths.
The findings were published in the scientific journal Histopathology in the study “Diagnostic utility of BAP1 and EZH2 expression in malignant mesothelioma.”
They suggest that a combination of these two biomarkers can be used as tools to improve the diagnostic accuracy of malignant mesothelioma.
Malignant mesothelioma is a highly aggressive cancer usually diagnosed at advanced stages. Diagnosis of this disease is still a challenge due to a lack of reliable and specific biomarkers.
Recent studies have found that 27 percent to 67 percent of malignant mesothelioma cases lack BAP1 protein expression, suggesting BAP1 as a possible biomarker to diagnose mesothelioma patients. This is particularly evident in epithelioid malignant mesothelioma (EMM) cases, 77 percent of which show loss of BAP1 expression, while only 0 to 15 percent of sarcomatoid malignant mesothelioma (SMM) cases show this alteration.
BAP1 loss has been associated with increased expression of a protein called EZH2, an inducer of cellular growth that has been linked to several cancers and which is usually associated with poor prognosis.
Although some studies have suggested EZH2 deregulation in malignant mesothelioma, its expression and association with BAP1 have not been fully understood. Now, researchers aimed to clarify these aspects and evaluate BAP1 and EZH2 as potential biomarkers for mesothelioma diagnosis.
The researchers studied samples from 32 patients with malignant mesothelioma and 44 patients with benign mesothelial proliferative lesions. Analysis of BAP1 and EZH2 levels showed that 53 percent of the malignant mesothelioma cases had loss of BAP1, and 22 percent had high levels of EZH2. None of the benign lesions presented such alterations.
No associations between BAP1 or EZH2 levels with clinical parameters such as age, sex, tumor location, history of asbestos exposure, and treatment were found.
But researchers found that the combined analysis of BAP1 and EZH2 levels could help differentiate epithelioid/biphasic malignant mesothelioma from benign mesothelial lesions with very high sensitivity and specificity (90 percent).
Analysis of the overall survival of the patients showed that loss of BAP1 was associated with better prognosis. High EZH2 levels, however, did not impact mesothelioma patients’ survival in this study. Still, researchers suggest that an analysis with a bigger cohort should be performed to confirm these results.
“Both BAP1 loss and high EZH2 expression were highly specific to malignant mesothelioma in differentiating from benign mesothelial proliferations,” the researchers wrote. “Combination of BAP1 and EZH2 improved the diagnostic accuracy, especially in EMM [epithelioid malignant mesothelioma] and BMM [biphasic malignant mesothelioma].”