Molecular events in endometrial carcinosarcomas and the role of high mobility group AT-hook 2 in endometrial carcinogenesis
Por:
Romero-Perez, L, Castilla, MA, Lopez-Garcia, MA, Diaz-Martin, J, Biscuola, M, Ramiro-Fuentes, S, Oliva, E, Matias-Guiu, X, Prat, J, Cano, A, Moreno-Bueno, G, Palacios, J
Publicada:
1 feb 2013
Resumen:
The 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. (c) 2013 Elsevier Inc. All rights reserved.
Filiaciones:
Romero-Perez, L:
Univ Seville, CSIC, Hosp Univ Virgen del Rocio, Inst Biomed Sevilla IBiS,Dept Pathol, Seville 41013, Spain
Castilla, MA:
Univ Seville, CSIC, Hosp Univ Virgen del Rocio, Inst Biomed Sevilla IBiS,Dept Pathol, Seville 41013, Spain
Lopez-Garcia, MA:
Univ Seville, CSIC, Hosp Univ Virgen del Rocio, Inst Biomed Sevilla IBiS,Dept Pathol, Seville 41013, Spain
Diaz-Martin, J:
Univ Seville, CSIC, Hosp Univ Virgen del Rocio, Inst Biomed Sevilla IBiS,Dept Pathol, Seville 41013, Spain
Biscuola, M:
Univ Seville, CSIC, Hosp Univ Virgen del Rocio, Inst Biomed Sevilla IBiS,Dept Pathol, Seville 41013, Spain
Ramiro-Fuentes, S:
Univ Seville, CSIC, Hosp Univ Virgen del Rocio, Inst Biomed Sevilla IBiS,Dept Pathol, Seville 41013, Spain
Oliva, E:
Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA
Matias-Guiu, X:
Univ Lleida, IRBLLEIDA, Hosp Univ Arnau de Vilanova, Dept Pathol & Mol Genet, Lleida 25198, Spain
Prat, J:
Hosp Santa Creu & Sant Pau, Dept Pathol, Barcelona 08025, Spain
Cano, A:
Inst Invest Sanitaria La Paz, Inst Invest Biomed Alberto Sols, Dept Bioquim, CSIC UAM,UAM,IdiPAZ, Madrid 28046, Spain
Moreno-Bueno, G:
Inst Invest Sanitaria La Paz, Inst Invest Biomed Alberto Sols, Dept Bioquim, CSIC UAM,UAM,IdiPAZ, Madrid 28046, Spain
Fdn MD Anderson Canc Ctr Madrid, Madrid 28033, Spain
Palacios, J:
Univ Seville, CSIC, Hosp Univ Virgen del Rocio, Inst Biomed Sevilla IBiS,Dept Pathol, Seville 41013, Spain
Hosp Univ Ramon y Cajal, Dept Pathol, Madrid 28031, Spain
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