Role of epithelial-mesenchymal transition factors in the histogenesis of uterine carcinomas
| Autor: | Anne Pierre Morel, Pierre De Saint Hilaire, Isabelle Ray-Coquard, Alain Puisieux, Mojgan Devouassoux-Shisheboran, Emeline Durieux, Tatiana Franceschi |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Epithelial-Mesenchymal Transition Estrogen receptor Histogenesis Biology Pathology and Forensic Medicine 03 medical and health sciences 0302 clinical medicine Carcinosarcoma Carcinoma medicine Biomarkers Tumor Humans Epithelial–mesenchymal transition Molecular Biology Retrospective Studies Zinc Finger E-box Binding Homeobox 2 Transdifferentiation Twist-Related Protein 1 Nuclear Proteins Zinc Finger E-box-Binding Homeobox 1 Cell Biology General Medicine Cell Dedifferentiation medicine.disease Immunohistochemistry Endometrial Neoplasms Serous fluid 030104 developmental biology Hormone receptor 030220 oncology & carcinogenesis Uterine Neoplasms Cancer research Female Neoplasm Grading PAX8 Carcinoma Endometrioid |
| Zdroj: | Virchows Archiv : an international journal of pathology. 475(1) |
| ISSN: | 1432-2307 |
| Popis: | Several subtypes of high-grade endometrial carcinomas (ECs) contain an undifferentiated component of non-epithelial morphology, including undifferentiated and dedifferentiated carcinomas and carcinosarcomas (CSs). The mechanism by which an EC undergoes dedifferentiation has been the subject of much debate. The epithelial–mesenchymal transition (EMT) is one of the mechanisms implicated in the transdifferentiation of high-grade carcinomas. To improve our understanding of the role of EMT in these tumors, we studied a series of 89 carcinomas including 14 undifferentiated/dedifferentiated endometrial carcinomas (UECs/DECs), 49 CSs (21 endometrial, 29 tubo-ovarian and peritoneal), 17 endometrioid carcinomas (grade 1–3), and 9 high-grade serous carcinomas of the uterus, using a panel of antibodies targeting known epithelial markers (Pan-Keratin AE1/AE3 and E-cadherin), mesenchymal markers (N-cadherin), EMT transcription factors (TFs) (ZEB1, ZEB2, TWIST1), PAX8, estrogen receptors (ER), progesterone receptors (PR), and the p53 protein. At least one of the three EMT markers (more frequently ZEB1) was positive in the sarcomatous component of 98% (n = 48/49) of CSs and 98% (n = 13/14) of the undifferentiated component of UEC/DEC. In addition, 86% of sarcomatous areas of CSs and 79% of the undifferentiated component of UEC/DEC expressed all three EMT-TFs. The expression of these markers was associated with the loss of or reduction in epithelial markers (Pan-keratin, E-cadherin), PAX8, and hormone receptors. In contrast, none of the endometrioid and serous endometrial carcinomas expressed ZEB1, while 6% and 36% of endometrioid and 11% and 25% of serous carcinomas focally expressed ZEB2 and TWIST1, respectively. Although morphologically different, EMT appears to be implicated in the dedifferentiation in both CSs and UEC/DEC. Indeed, we speculate that the occurrence of EMT in a well differentiated endometrioid carcinoma may consecutively lead to a dedifferentiated and undifferentiated carcinoma, while in a type II carcinoma, it may result in a CS. |
| Databáze: | OpenAIRE |
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