Epithelial-to-mesenchymal transition in malignant mesothelioma

Epithelial-to-mesenchymal transition EMT is a molecular-cellular process activated during embryonic development and tissue remodelling, by which epithelial cells lose their polarity and cell contacts, acquire the expression of mesenchymal markers and manifest a migratory phenotype. The progressive loss of E-cadherin is coupled with expression of non-epithelial cadherins, process known as “cadherin switching”. As tumours often mimic embryonic development, it has been postulated that EMT represents a transient event in carcinomas progession. Malignant Mesothelioma MM could represent an EMT in vivo model, because tumor cells can exhibit epithelial, sarcomatous and biphasic differentiation. Forty five patients with MM were investigated by immunohistochemical expression of cadherins E,N,P,11,p120 catenin,SPARC and caveolin in two tissue microarrays. Protein expression was scored from 0 to 3 in tumour and stroma. Data were correlated with histologic patterns, thoracoscopy findings and survival. E-P cadherins expression was observed in 79,3% of epithelial MM without evidence in mesenchymal component of mixed and sarcomatous types. N-11cadherins were detected in 20,6%, 29.4% and 17.6% of these histotypes,respectively.The mesenchymal markers were detected in 100% of sarcomatous and mixed MM and in a many samples of epithelial group. Immunohistochemical data correlated with metastatic status, multi-focal disease and poor survival, showed, in epithelial MM forms, weak or absent E-Pcadherins expression, while N-11cadherins, mesenchymal markers and P120 catenin were observed. Our results suggest that the aggressiveness of MM,could be explained by the acquisition of a mesenchymal phenotype in the context of EMT