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Earlier diagnosis for people with mesothelioma – translational cancer research study

The study is ‘BAP1 immunohistochemistry as a clinically useful diagnostic test for mesothelioma in the routine surgical pathology laboratory’.

Led by Professor Anthony Gill at Sydney Vital, it is helping people with mesothelioma get earlier diagnosis.

About the author

Professor Anthony Gill is Professor of Surgical Pathology at the University of Sydney and a specialist surgical pathologist at Royal North Shore Hospital.

He has particular research interest in hereditary cancer syndromes, endocrine pathology, lung pathology and gastrointestinal pathology.

He has a special emphasis on translating advances in knowledge gained about cancer at the basic science level into clinically useful diagnostic tests.

Professor Anthony Gill

Who is the study aiming to help?

The study is aiming to help people with mesothelioma. Over 200 people die from mesothelioma in NSW every year, all of whom are aged 45 and over.

What is the issue?

The diagnosis of mesothelioma is very commonly made late, after people have had symptoms for a long time.

If fluid accumulates around the lung it can be very difficult for doctors to tell whether this is caused by mesothelioma or some other process.

Symptoms consistent with mesothelioma include:

  • shortness of breath, usually worse with activity or when lying down
  • chest pain, or pain in the shoulder and upper arm
  • loss of appetite, or loss of weight
  • persistent cough, or a change in cough
  • heavy sweating occuring particularly at night.

What is the study doing?

It was recently found that about half of mesotheliomas are associated with a mutation in the DNA of tumours which damages a protein called BRCA 1 Associated Protein 1 (BAP1).

BAP1 mutations occur very rarely in any other settings. Therefore if mutations in BAP1 are found it could confirm a diagnosis of mesothelioma.

Fig 1: Mesothelioma cells showing loss of BAP1 expression

Fig 1 - Mesothelioma cells showing loss of BAP1 expression

Unfortunately conventional BAP1 testing is very expensive and time consuming and could not be performed in the routine clinical setting for all patients with mesothelioma.

Professor Anthony Gill and his team developed a new approach to testing for mesothelioma using immunohistochemistry for BAP1.

It is very cheap and can be performed in almost any pathology laboratory at very little additional cost.

They found in half of mesothelioma cases, BAP1 expression is lost and that BAP1 loss never occurs in benign mesothelial disease. 

That means that if the test finds loss of BAP1 in cells, a confident diagnosis of mesothelioma can be made – usually much earlier than it can be with any other test.

What kind of care is now being offered to people with mesothelioma?

Making a definitive diagnosis early allows treatment to be started as early as possible, and that's important in every malignancy.

What’s next?

Now BAP1 testing is in routine clinical use, Professor Gill is helping other laboratories to establish the testing locally so that samples do not need to be sent to centralized laboratories for testing.

What is the role of Sydney Vital?

The study is almost entirely funded by Sydney Vital.

“My protected research time, which is 0.3 full time equivalent, is entirely funded by Sydney Vital,” Professor Gill says.

“Our research scientific officer, Loretta Sioson, who did a lot of technical work for this study, is entirely funded by Sydney Vital through a Research Infrastructure Grant.”

Fig 1: Mesothelioma cells which show loss of BAP1 expression have grey nuclei (arrows) with BAP1 immunohistochemical testing whereas benign cells in the background have brown coloured nuclei. This loss of BAP1 expression is used to definitively diagnosis mesothelioma much earlier than was previously possible.

What outcomes are coming from this study?

What outcomes are coming from this study?

So far in Professor Anthony Gill’s department alone, BAP1 testing has been performed on 278 people in 2017 – about 40 of which were confirmed to have mesothelioma.

In many of these people, without BAP1 testing a diagnosis of mesothelioma could not have been made until the disease was more advanced.

Professor Gill says it has now become standard of care in diagnostic pathology laboratories in Australia and around the world.

“There were several groups working on the same thing around the world, and we were the first/equal first to actually be able to validate this and deliver it as a diagnostic test in the routine clinical setting.”

“Now around the world BAP1 immunohistochemistry is accepted as a diagnostic test and every new group who studies it concludes the same thing – that it works!” he explains.

What’s next?

Now BAP1 testing is in routine clinical use, Professor Gill is helping other laboratories to establish the testing locally so that samples do not need to be sent to centralized laboratories for testing.

What is the role of Sydney Vital?

The study is almost entirely funded by Sydney Vital.

“My protected research time, which is 0.3 full time equivalent, is entirely funded by Sydney Vital,” Professor Gill says.

“Our research scientific officer, Loretta Sioson, who did a lot of technical work for this study, is entirely funded by Sydney Vital through a Research Infrastructure Grant.”

 

Fig 1: Mesothelioma cells which show loss of BAP1 expression have grey nuclei (arrows) with BAP1 immunohistochemical testing whereas benign cells in the background have brown coloured nuclei. This loss of BAP1 expression is used to definitively diagnosis mesothelioma much earlier than was previously possible.