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

Abstract

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.

• Authors: Laura Romero-Pérez, María Ángeles Castilla, María Ángeles López-García, Juan Díaz-Martín, Michele Biscuola, Susana Ramiro-Fuentes, Esther Oliva, Xavier Matias-Guiu, Jaime Prat, Amparo Cano, Gema Moreno-Bueno, José Palacios
• Journal: Human pathology (Hum Pathol) Vol. 44 Issue 2 Pg. 244-54 (Feb 2013) ISSN: 1532-8392 [Electronic] United States
• PMID: 22974476 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier Inc. All rights reserved.

Chemical References

• Biomarkers, Tumor
• DNA-Binding Proteins
• HMGA2 Protein
• LIN28B protein, human
• MicroRNAs
• RNA, Messenger
• RNA, Neoplasm
• RNA-Binding Proteins
• mirnlet7 microRNA, human

Topics

• Biomarkers, Tumor (genetics, metabolism)
• Carcinoma, Endometrioid (genetics, metabolism, pathology)
• Carcinosarcoma (genetics, metabolism, pathology)
• Cell Differentiation
• Cell Line, Tumor
• Cell Transformation, Neoplastic
• DNA-Binding Proteins (genetics, metabolism)
• Endometrial Neoplasms (genetics, metabolism, pathology)
• Epithelial-Mesenchymal Transition
• Female
• Gene Expression Profiling
• Gene Expression Regulation, Neoplastic
• HMGA2 Protein (genetics, metabolism)
• Humans
• Immunohistochemistry
• MicroRNAs (genetics, metabolism)
• Oligonucleotide Array Sequence Analysis
• RNA, Messenger (genetics)
• RNA, Neoplasm (genetics)
• RNA-Binding Proteins
• Real-Time Polymerase Chain Reaction
• Tissue Array Analysis