malignant mixed müllerian tumours

Malignant mixed müllerian tumours (MMMT), also referred to as uterine carcinosarcomas or sarcomatoid carcinomas, are rare uterine tumours accounting for less than 5% of EC.

Molecular studies have suggested recently that MMMT should be regarded as metaplastic carcinomas.

Like sarcomatoid carcinomas of other locations, carcinosarcomas probably result from endometrial carcinomas through epithelial-to-mesenchymal transition (EMT).

EMT is a process of cellular transdifferentiation in which epithelial cells lose polarity and cell–cell contacts, reorganize their cytoskeleton, acquire expression of mesenchymal markers and manifest a migratory phenotype.

EMT can be induced by different signals and pathways, such as those mediated by transforming growth factor (TGF)-β, tyrosine kinase receptors and/or Wnt, depending on the specific cellular context.

Activation of one or more of these pathways converges frequently in a group of transcription factors, Snail1, Slug, ZEB1, ZEB2, E47, E2-2 and Twist, most of them with the ability to repress E-cadherin, a master regulator of cell adhesion and polarity.

While the transient presence of EMT features is important for myometrial invasion in conventional endometrial carcinomas, MMMT show permanent expression of these features leading to repression of epithelial markers (E-cadherin) and increased expression of mesenchymal markers, including proteins involved in skeletal muscle development.

All these molecular changes are responsible for the appearance of the sarcomatous areas as well as the presence of heterologous elements. It has been shown recently that MMMT show a microRNA signature typical of EMT.

Credits

 Molecular pathology of endometrial carcinoma. Matias-Guiu X, Prat J.
Histopathology. 2013 Jan;62(1):111-23. doi : 10.1111/his.12053 PMID: 23240673