BioEvolution ISBN 978-81-925781-3-2, May 2014, pg 24-27 www.giapjournals.org/bioevolution.html Page 24 MESOTHELIOMA : CURRENT PROSPECTIVES Hema Madhav 1 and Navkiran Kaur* 1 Student, B.Sc (Hons) Medical Biotechnology *Assistant Professor, Amity Institute of Biotechnology, Amity University, Noida navkirank@amity.edu INTRODUCTION Mesothelioma are rare type of cancer in which malignant cells are found in the lining of the chest or abdomen, Majority of the patients diagnosed with mesothelioma are those who traced to job-related exposure to asbestos. The disease can take anywhere from 20 to 50 years after exposure to asbestos before it shows obvious symptoms and an oncologist can make a definitive diagnosis. Mesothelioma has been described as an insidious neoplasm because of its long latency period. It arises in the mesothelial surfaces of tissues in the pleura but can also occur in the peritoneum and the tunica vaginalis. While no cure for the disease exists and the prognosis is typically poor, researchers made significant progress in recent years in understanding mesothelioma and developing new treatment options and alternative therapies. As estimated by WHO millions are dying of Asbestos related diseases each year. In India, Bihar chief Minister has demanded to ban Asbestos completely. Indian Association of Occupational Health is also in favor of complete ban on Asbestos. TYPES OF MESOTHELIOMA There are three types of mesothelioma (i) pleural mesothelioma (ii) peritoneal mesothelioma (iii) pericardial mesothelioma. The chest abdomen and heart are surrounded by a membrane called mesothelium. This membrane is important for the movements (contraction or expansion) of heart lungs and stomach. The cancers which arise in mesothelial membrane are called malignant mesothelioma. The inhaled asbestos will cause inflammation to the surrounding lung tissue where they get lodged and cause irritation. Further, it leads to the production and secretion of various chemical substance called cytokines. These cytokines induce various inter cellular changes to lungs mesothelia cells. Hence, the interaction of asbestos fiber with combination of cytokines causes the cell to precede malignant pathway. This inturn switch on the pro-growth genes and may lead to uncontrolled cell division and develop mutations, which finally develop into malignant mesothelioma. MOLECULAR PATHOGENESIS There is an established association between asbestos and respiratory diseases for decades. The risk of developing mesothelioma was described as 10% over the lifetime of an asbestos worker, with up to 70% of all mesothelioma cases involving documented asbestos exposure. Concomitant smoking enhances the risk of malignancy in an asbestos worker, with a 60-fold increased risk of developing non–small cell lung cancer. The chance of dying of a malignancy (mesothelioma or lung cancer) versus a nonmalignant cause is 50% in an individual exposed to asbestos compared to 18% in an individual not exposed. The majority of asbestos fibers are either amphibole (sharp, rod-like) or serpentine. The serpentine fibers contribute more towards the carcinogenicity than the amphibole type. Inhaled asbestos fibers are trapped in the lower third of the lung, where they initiate an inflammatory response. The fibers are phagocytosed into mesothelial cells and initiate an oncogenic cascade of events that includes activation of c-Myc and c-Jun oncogenes, binding with epidermal growth factor receptors (EGFRs), and promotion of anti apoptotic genes such as Bcl-xl.5. The Simian Virus SV-40 is a polyomavirus that is thought to inactivate tumor suppressor genes of the retinoblastoma family. SV-40 nucleic acids have been identified in mesothelioma cases without exposure to asbestos. Abnormalities in chromosomes 1, 3, 6 and 9 can also be observed in patients with this disorder. Occasionally, loss of one copy of ch.22 may be observed. Now it is discovered that there is a germ line mutations in the gene encoding BRCA1 associated protein-1 (BAP1) [6] . PATHOLOGY Pathologically, there is considerable difficulty in diagnosing mesothelioma due to the tissue obtained after biopsy is often minimal and may not be adequate to perform the necessary array of tests to distinguish mesothelioma from other pleural-based malignancies. Histological variability made the diagnosis very challenging. Histological variable types of mesothelioma have been identified and can be correlated well with the diagnosis and prognosis of the disease. These types include epithelioid which is associated with the good prognosis and sarcomatoid variants with characteristic spindle morphology are associated with a worse prognosis. Often, mixed epithelioid and sarcomatoid histology can be seen. Tissue obtained by cytological analysis of pleural fluid or blind pleural biopsy is limited and it is very difficult to classify the mesothelioma on the basis of the correct histology. Hence,