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Dr. Michele Carbone's Scientific Publications

Mesothelioma: Scientific clues for prevention, diagnosis, and therapy

Mesothelioma: Scientific clues for prevention, diagnosis, and therapy

Published in Ca: A Cancer Journal for Clinicians, online version on July 9, 2019

Mesothelioma affects mostly older individuals who have been occupationally exposed to asbestos. The global incidence and mortality rates are unknown, because data are not available from developing countries that continue to use large amounts of asbestos. The rate of mesothelioma has decreased in Australia, the United States, and Western Europe, where the use of asbestos was banned or strictly regulated in the 1970s and 1980s, demonstrating the value of these preventive measures. However, in these same countries, the overall number of deaths from mesothelioma has not decreased as the size of the population and the percentage of old people have increased. Moreover, hotspots of mesothelioma may occur when carcinogenic fibers that are present in the environment are disturbed as rural areas are being developed. Novel immunohistochemical and molecular markers have improved the accuracy of diagnosis; however, about 14% (high-resource countries) to 50% (developing countries) of mesothelioma diagnoses are incorrect, resulting in inadequate treatment and complicating epidemiological studies. The discovery that germline BRCA1-associated protein 1 (BAP1) mutations cause mesothelioma and other cancers (BAP1 cancer syndrome) elucidated some of the key pathogenic mechanisms, and treatments targeting these molecular mechanisms and/or modulating the immune response are being tested.  The role of surgery in pleural mesothelioma is controversial as it is difficult to predict who will benefit from aggressive management, even when local therapties are added to existing or novel systemic treatments. Treatment outcomes are improving, however, for peritoneal mesothelioma. Multidisciplinary international collaboration will be necessary to improve prevention, early detection, and treatment.
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Diagnostic and prognostic biomarkers for malignant mesothelioma: an update

Diagnostic and prognostic biomarkers for malignant mesothelioma: an update

published in Translational Lung Cancer Research, June 16, 2017

A review of the most promising biomarkers for early detection of malignant mesothelioma.
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Mesothelioma: Recent Highlights

Mesothelioma: Recent Highlights

Annals of Translational Medicine 2017: Review Article

Recent discoveries have elucidated some of the mechanisms responsible for the development of mesothelioma. 
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Malignant Mesothelioma: Time to Translate?

Malignant Mesothelioma: Time to Translate?

Opinion: Lessons from the Clinic

Malignant Mesothelioma is a rare and poorly understood cancer with limited therapeutic approaches.

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Positive nuclear BAP1 immunostaining helps differentiate non-small cell lung carcinomas from malignant mesothelioma

Positive nuclear BAP1 immunostaining helps differentiate non-small cell lung carcinomas from malignant mesothelioma

Differentiating between pleural malignant mesothelioma (MM) and lung cancer is often challenging. Immunohistochemical (IHC) stains used to distinguish these malignancies include markers  that are most often positive in malignant mesothelioma and less frequently positive in carcinomas, and vice versa. However, in 10 to 20% of the cases, the immunohistochemical staining results can be confusing and inconclusive,  and novel markers are sought to increase the diagnostic accuracy.

We stained 45 non-small cell lung cancers (32 adenocarcinomas and 13 squamous cell carcinomas) with a monoclonal antibody for BRCA1-associated protein 1 (BAP1) and also with an IHC panel we routinely use to help differentiate MM from carcinomas, which include calretinin, Wilms Tumor 1, cytokeratin 5, podoplantin D2-40, pankeratin CAM5.2, thyroid transcription factor 1, Napsin-A,  and p63.  Nuclear BAP1 expression was also analyzed in 35 MM biopsies. All 45 non-small cell lung cancer biopsies stained positive for nuclear BAP1, whereas 22/35 (63%)  MM biopsies lacked nuclear BAP1 staining, consistent with previous data. Lack of BAP1 nuclear staining was associated with MM. Focal BAP1 staining was observed in a subset of samples, suggesting polyclonality. Diagnostic accuracy of other classical IHC markers was in agreement with previous studies. Our study indicated that absence of nuclear BAP1 staining helps differentiate MM from lung carcinomas. We suggest that BAP1 staining should be added to the IHC panel that is currently used to distinguish these malignancies.  

 Authors: Michele Carbone, David Shimizu, Andrea Napolitano, Mika Tanji,  Harvey I. Pass, Haining Yang, Sandra Pastorino

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