Epithelial-Mesenchymal Transitions in Human Cancer

Abstract

Epithelial-mesenchymal transition (EMT) is a type of epithelial plasticity that is characterized by long-lasting morphological and molecular changes in epithelial cells as a result of transdifferentiation towards a mesenchymal cell type. To detect possible phenotypic transitions in human cancer, surgical pathology is a useful medical discipline, examining surgical or biopsy material at the microscopic and ultrastructural level. The expression in a particular tumor of epithelial and mesenchymal markers is evaluated by means of immunohistochemistry or in situ hybridization, and this could, besides directing to a correct diagnosis, substantiate a possible transdifferentiation. Whereas EMT occurs in several stages of embryonic development and can be readily induced in (cancer) cell lines in vitro, in human cancer the phenomenon is rarely encountered. Carcinosarcoma is the tumor best studied, in which monoclonality of both epithelial and mesenchymal cell components strongly favors an EMT. A challenging hypothesis considers EMT as a more general event, providing an additional survival advantage in all types of carcinoma. By means of EMT the epithelial tumor cells would transdifferentiate into myofibroblasts that lose their malignant phenotype but constitute the