Journal of Translational Medicine
Malignant mesothelioma (MM) is a very aggressive type of cancer, with a dismal prognosis and inherent resistance to chemotherapeutics. Development and evaluation of new therapeutic approaches is highly needed. Immunosuppressant FTY720, approved for multiple sclerosis treatment, has recently raised attention for its anti-tumor activity in a variety of cancers. However, its therapeutic potential in MM has not been evaluated yet.
We studied the effect of ethyl pyruvate (EP), the ethyl ester of pyruvic acid, on the malignant phenotype of MM cells in tissue culture and on tumor growth in vivo using an orthotopic MM xenograft model.
Mesothelioma: Causes, Prevention, Screening and Early Detection
The International Association for the Study of Lung Cancer (IASLC) sponsored a live 60-minute CME webinar on November 15, 2016 featuring Dr. Michele Carbone, MD, PhD and Dr. Harvey I. Pass, MD . The webinar describes clinical research efforts focusing on how mesothelioma prevention and intervention at earlier stages of the disease process may improve the management of mesothelioma.
Opinion: Lessons from the Clinic
Malignant Mesothelioma is a rare and poorly understood cancer with limited therapeutic approaches.
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