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Epithelial–mesenchymal transition in carcinomas of the female genital tract

Authors


Address for correspondence: Dr C J R Stewart, Department of Histopathology, King Edward, Memorial Hospital, Bagot Road, Subiaco, Perth, Western Australia 6008, Australia. e-mail: colin.stewart@health.wa.gov.au

Abstract

Invasion is a defining feature of malignancy, but the mechanisms of invasion in many common cancers, including gynaecological malignancies, remain unclear. However, it has been proposed that malignant cells may usurp a normal embryological process, epithelial–mesenchymal transition (EMT), as a means of acquiring migratory capacity. The synergistic role of the tumour microenvironment in EMT induction has also been explored and helps to explain the spatially restricted distribution of EMT at the deep tumour margin (invasive front). Furthermore, tumour cells undergoing EMT may acquire cancer stem cell characteristics, and this may be relevant to the entire metastatic process and to tumour recurrence and treatment failure. Nevertheless, doubts persist regarding the role of EMT in malignant progression in vivo, partly because few studies have correlated molecular and histological alterations in clinical pathology specimens. In the current review we summarize the evidence for EMT in the common gynaecological epithelial malignancies, and discuss the morphological and immunohistochemical changes occurring at the invasive tumour front that may represent EMT-like processes. The possibility that carcinosarcomas represent a variant type of EMT with ‘fixed’ mesenchymal differentiation is also considered. Diagnostic histopathologists are ideally placed to critically evaluate the role of EMT in gynaecological and other types of malignancy.

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