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Title

Molecular events in endometrial carcinosarcomas and the role of high mobility group AT-hook 2 in endometrial carcinogenesis

AuthorsRomero-Pérez, Laura; Castilla, María Ángeles; López-García, María Ángeles; Díaz-Martín, J. ; Biscuola, Michele; Ramiro-Fuentes, Susana; Oliva, Esther; Matías-Guiu, Xavier; Cano, Amparo ; Moreno-Bueno, Gema ; Palacios Calvo, José
Issue DateFeb-2013
PublisherElsevier
CitationHuman Pathology 44(2): 244-254 (2013)
AbstractThe molecular events implicated in the development of endometrial carcinosarcoma remain poorly understood. Using complementary DNA microarrays, we analyzed a group of 15 endometrial carcinosarcomas and compared their gene expression profiles with those obtained from a group of 23 endometrioid endometrial carcinomas. We demonstrated changes in the expression of genes modulating processes such as the epithelial to mesenchymal transition, muscle differentiation, the expression of cancer/testis antigens, and immune response in endometrial carcinosarcomas. The high mobility group AT-hook 2 gene is an embryonic nuclear factor that mediates epithelial to mesenchymal transition in various tumor models, and it was among the genes overexpressed in endometrial carcinosarcomas. High mobility group AT-hook 2 overexpression was confirmed in 54% of endometrial carcinosarcomas by quantitative real time-polymerase chain reaction and immunohistochemistry. Moreover, we found a significant inverse correlation between the expression of high mobility group AT-hook 2 and let-7b, a member of the let-7 family of microRNAs that represses high mobility group AT-hook 2 expression. These changes were also associated with overexpression of Lin28B, a suppressor of microRNA biogenesis that is implicated in cancer progression and metastasis. Finally, high mobility group AT-hook 2 overexpression, which was detected in less than 3% of endometrioid endometrial carcinomas, was observed in many nonendometrioid carcinomas (46% of 28 samples). This pattern of expression, restricted to nonendometrioid carcinomas and endometrial carcinosarcomas, reflects a role for high mobility group AT-hook 2 in endometrial carcinogenesis that is associated with aggressive phenotypes and points to its potential use as a marker to distinguish between endometrioid and nonendometrioid tumors. © 2013 Elsevier Inc.
Publisher version (URL)http://doi.org/10.1016/j.humpath.2012.05.013
URIhttp://hdl.handle.net/10261/77395
DOI10.1016/j.humpath.2012.05.013
Identifiersissn: 0046-8177
e-issn: 1532-8392
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