title: 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.affiliation: Department of Pathology, Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, 41013 Sevilla, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Romero-Pérez
authors.forename: María Ángeles
authors.initials: MÁ
authors.lastname: Castilla
authors.forename: María Ángeles
authors.initials: MÁ
authors.lastname: López-García
authors.forename: Juan
authors.initials: J
authors.lastname: Díaz-Martín
authors.forename: Michele
authors.initials: M
authors.lastname: Biscuola
authors.forename: Susana
authors.initials: S
authors.lastname: Ramiro-Fuentes
authors.forename: Esther
authors.initials: E
authors.lastname: Oliva
authors.forename: Xavier
authors.initials: X
authors.lastname: Matias-Guiu
authors.forename: Jaime
authors.initials: J
authors.lastname: Prat
authors.forename: Amparo
authors.initials: A
authors.lastname: Cano
authors.forename: Gema
authors.initials: G
authors.lastname: Moreno-Bueno
authors.forename: José
authors.initials: J
authors.lastname: Palacios
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D018269:Carcinoma, Endometrioid / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002296:Carcinosarcoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D016889:Endometrial Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D025743:HMGA2 Protein / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D016601:RNA-Binding Proteins; D060888:Real-Time Polymerase Chain Reaction; D046888:Tissue Array Analysis
chemical_list: D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D025743:HMGA2 Protein; C516326:LIN28B protein, human; D035683:MicroRNAs; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D016601:RNA-Binding Proteins; C487931:mirnlet7 microRNA, human