Malignant mesothelioma show diverse histopathological features, making it more diffcult to make accurate diagnosis or differentiating from other cancers. The use of immunohisotchemical technique has improved the accuracy of pathological diagnosis in many of cases. Howerver, there are still no proper conscience among the pathologists with expertise in mesothelioma diagnosis in some of the difficult cases (False Negative or False positive) with recent immunohistochemical data interpretations.
In Japan, we found about 15% of misdiagnosis of malignant mesothelioma (Takeshima et al., Lung Cancer, 66(2) : 191-197, 2009) by general pathologists. To improve the accuracy of pathological diagnosis of malignant mesothelioma even by general pathologists who are not expert in mesthelioma diagnosis, search of better immunohistochemical markers are essential.
Differential microRNA expression profiling of mesothelioma and expression analysis of miR-1 and miR-214 in mesothelioma.
Malignant mesothelioma is a highly aggressive cancer with poor prognosis and refractory to currently available therapies. Most of the patients with advanced invasive nature are not amenable to surgical resection and/or available anticancer therapy, thus development of novel effective therapeutic regimes is needed. Aberrant expression of microRNAs (miRNAs) has been proposed to contribute to carcinogenesis and aggressiveness of mesothelioma. We analyzed miRNA expression in mesothelioma cell lines using TaqMan miRNA expression array and found significant number of miRNAs, which showed increased or lost expression. We validated the increased expression of miR-182, and miR-183 in mesothelioma cell lines by individual miRNA assays and SmartFlare miRNA probes. We further investigated the miR-1, and miR-214, which were not expressed in mesothelioma cells by real-time RT-PCR. Transfection of mesothelioma cells, ACC-Meso-1 and CRL5915, with miRNA mimic (hsa-miR-1 mimic and hsa-miR-214 mimic) led to inhibition of cell growth, invasion and migration. We paid attention to PIM1, the target gene of both miR-1 and miR-214 miRNAs and which was found overexpressed in mesothelioma cells, and miR-1 and miR-214 mimic transfection of mesothelioma cell lines showed downregulation of PIM1 by western blot analysis. The miRNAs, miR-1 and miR-214, may play a role in carcinogenesis of mesothelioma thus might be considered as candidate therapeutic targets in mesothelioma.
Malignant mesothelioma is an aggressive cancer arising from mesothelial lining of pleura, peritoneum, pericardium, and tunica vaginalis. Asbestos exposure is considered as a principal cause of malignant mesothelioma.
In Japan, the incidence of malignant mesothelioma is increasing year by year and have reached more than 1400 death per year. Many of these patients had history of occupational exposure of asbestos (80~90%) and others areconsidered due to environmental exposure (e.g. residence near asbestos factory).
Kushitani K, Takeshima Y, Amatya VJ, Furonaka O, Sakatani A, Inai K.
Pathology International, 58(2) : 75-83, 2008
Practice for Medical Research