Background: Uterine sarcomas are rare mesodermic tumors that represent approximately 3% of all uterine cancers. They display histological diversity and aggressive behavior, with early dissemination and high mortality when compared with epithelial tumors. Due to their diversity and rarity, there is no consensus related to risk factors for poor prognostic and appropriated treatment. The knowledge of the gene expression regulation can contribute to a better understanding of these neoplasms. Recently it was demonstrated an essential role for the forkhead transcription factor FOXO3 in the regulation of diverse cellular functions and tumors development. Our aim was to study the expression profile of the transcription factor FOXO3 in several histological types of uterine sarcoma. Method: we evaluated 100 samples of uterine sarcomas (including leiomyosarcomas, carcinosarcomas, adenosarcomas and endometrial stromal sarcomas), leiomyomas and myometrium obtained from patients during the period of 2000 to 2012. FOXO3 protein expression was assessed by immunohistochemistry. mRNA expression was evaluated by quantitative Real Time PCR. The results were submitted to statistical analyses together with patient's data. Results: We observed that carcinosarcomas (CSS) and adenosarcomas (ADS) showed the highest FOXO3 protein signal, considering exclusively the mesenchymal component. Concerning to muscular tumors (leiomyoma and leiomyosarcoma), we found an increasing enhancement of this protein expression from the myometrium to myoma and leiomiosarcoma, both in protein and transcriptional levels. Statistical analysis showed that tumors with weak or lack of FOXO3 protein present poor prognosis, regardless of their histological type. Conclusion: FOXO3 protein expression seems to be a relevant role in uterine sarcomas, however further analyses are needed.

Citation Format: Thais G. Almeida, Natalia Garcia, Isabela W. Cunha, Glauco Baiocchi, Fernando A. Soares, Gustavo A. Maciel, Edmund C. Baracat, Katia C. Carvalho. Lack of expression of FOXO3 correlates with poor prognosis on uterine sarcomas. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4822. doi:10.1158/1538-7445.AM2015-4822