Gene Test May Help Distinguish Pleural Mesothelioma from Lung Cancer

There is more evidence this week that the tumor suppressor gene known as BRCA1-associated protein 1 (BAP1) could help doctors distinguish pleural mesothelioma from other types of lung cancer – even cancers that commonly spread to the pleura.

Pleural mesothelioma is unique among cancers in that it starts on the pleural membrane that surrounds the lungs.

When other types of cancers metastasize to this region, however, it can be nearly impossible to tell them apart. Especially since late-stage pleural mesothelioma also shares many of the same symptoms as lung cancer, including cough, chest pain, and fatigue.

But a team of pathologists in British Columbia has found that, despite their similarities, malignant mesothelioma and lung cancer can be very different in their expression of BAP1.

BAP1 Expression and Mesothelioma

The BAP1 protein, which is supposed to help suppress the growth of tumors, is produced by the BAP1 gene.

Among people who carry a mutation on this gene (also called BAP1 Cancer Syndrome) and do not produce the BAP1 protein, scientists have demonstrated a higher susceptibility to mesothelioma.

The bottom line for these people is that, if they are exposed to asbestos, they are much more likely to receive a mesothelioma diagnosis than are other asbestos-exposed individuals. An understanding of the role of BAP1 in mesothelioma has helped doctors understand why only a small fraction of people exposed to asbestos get mesothelioma.

Mesothelioma or Lung Cancer?

Although non-small cell lung cancer and pleural mesothelioma do share certain characteristics, the two have different patterns of growth and metastasis and respond differently to treatment. For this reason, it is vital for doctors to make a definitive diagnosis as early as possible so that they can implement the best treatment.

In the newest study on BAP1 and lung cancer, researchers with Vancouver General Hospital, Abbotsford Regional Hospital, and the British Columbia Cancer Agency tested for BAP1 expression in 133 patients with non-small cell lung cancer.  

They found that only one percent of the lung cancer patients tested had cancer cells that exhibited BAP1 loss.

“We conclude that loss of BAP1 expression is a rare event in non-small cell lung cancer,” writes Vancouver pathologist and study author Daniel Owen, MD. “Therefore, BAP1 is a potentially useful addition to the immunohistochemical markers used to distinguish mesothelioma from pleural metastasis of non-small cell lung cancer.”

Dr. Michele Carbone with the University of Hawaii and his colleagues reached a similar conclusion last year. In their study published in Oncotarget, none of the lung cancer patients showed BAP1 loss while 63 percent of malignant mesothelioma patients did.  

Previous studies of BAP1’s role in mesothelioma have uncovered one bright spot: Although people with familial BAP1 mutations are more likely to develop mesothelioma (and several other types of cancer), they also have better odds of surviving mesothelioma.

Source:

Owen, D, et al, “Loss of BRCA1-associated Protein 1 (BAP1) Expression is Rare in Non-Small Cell Lung Cancer”, February 2017, Human Pathology, pp. 82-85

Carbone, M, et al, “Positive nuclear BAP1 immunostaining helps differentiate non-small cell lung carcinomas from malignant mesothelioma”, July 18, 2016, Oncotarget

Baumann, F, et al, “Mesothelioma Patients with Germline BAP1 Mutations have Seven=Fold Improved Long-term Survival”, November 7, 2014, Carcinogenesis