Molecular analysis of the mechanisms involved in the regulation of EGF, VEGF, HER2 and of the transcriptional factor Foxo3 expression in uterine sarcoma

Abstract

Uterine sarcomas are rare mesodermic tumors that include approximately 3% of all uterine cancers. They show histological diversity and aggressive behavior, with early dissemination and high mortality when compared with epithelial tumors. The prognostic is variable, with five years survival rate ranging between 10% and 50%. Because its diversity and rarity, there is no consensus related to risk factors for poor prognostic and appropriated treatment. In this sense, the knowledge of the gene expression regulation can contribute to a better understanding of these neoplasms and to aid the diagnosis and prognostic of their different histological types. Some studies report the expression of growth factors and their receptors in different histological types of sarcoma and was recently demonstrated an essential role for the transcription factor FOXO3 in the regulation of diverse cellular functions. Here, we will evaluate the molecular mechanisms that may be involved in regulation of the growth factors EGF, VEGF, HER2 and transcription factor FOXO3 expression in different histological types of uterine sarcoma. For this, we will use 100 samples of uterine sarcomas (including leiomyosarcomas, carcinosarcomas, adenosarcomas and endometrial stromal sarcomas) obtained from patients during the period of 2000 to 2010. The protein expression of these markers will be analyzed by immunohistochemistry. The promoter methylation and mutation previously in the literature will be evaluated by DNA sequencing. Gene amplification or deletion will be assessed by Fluorescent in situ hybridization (FISH). miRNA expression will be analyzed by quantitative Real Time PCR (qRT-PCR). All results will be submitted to statistical analyses together with patient's data. (AU)