Abstract 4882: Differential BMP4 and GREM1 protein expression in uterine leiomyosarcoma and leiomyoma.

Abstract

Abstract Background: Uterine leiomyosarcoma (ULMS) and leiomyoma (ULM) are smooth muscle tumors with distinct clinical behavior. Little is known about the factors that influence these tumors biology. Differential diagnosis among low grade ULMS and the several clinical forms of ULM is a challenge both in laboratory and pathological routine. Thus, the identification of new molecular markers can help in the differential diagnosis between ULM from ULMS and clinical management. Our aim was to evaluate expression of bone morphogenetic protein - 4 (BMP-4) and Gremlin-1 (GREM1) in uterine leiomyosarcoma and leiomyoma (including leiomyoma with atypia) using immunohistochemistry. Method: 57 patients with ULMS and 30 with ULM, among them 10 ULM with atypia (ULMA) were select. The tissues were used in tissue microarray construction. Immunohistochemistry reaction was performed with monoclonal antibody against BMP-4 and GREM-1 and evaluated using semi-quantitative method. Results: BMP-4 was positive in 43% of the ULMS, 5% ULM and 80% ULMA, respectively. GREM-1 was positive in 67% of the ULMS, 20% ULM and 10% ULMA. BMP-4 is a potent growth factor that is involved in many important biological processes. Gremlin-1 can specifically bind to BMP-4 precursor protein inside cells, which prevents the production and secretion of mature BMP-4. This regulation determines BMP-4 biological effects on cells in the local microenvironment. However, the molecular mechanism of GREM-1/BMP-4 interaction remains unexplored. Conclusion: Ours preliminary results showed that expression of BMP-4 and GREM-1 play an important role in uterine smooth tumors, in while atypical leiomyomas presented higher levels of BMP-4 protein expression and lower levels of GREM-1. However, the role of these proteins interactions must be clarified. Citation Format: Natalia Garcia, Faila Catarina Souza, Isabela Werneck Cunha, Fernando Augusto Soares, Gustavo Arantes Rosa Maciel, Edmund Chada Baracat, Katia Candido Carvalho. Differential BMP4 and GREM1 protein expression in uterine leiomyosarcoma and leiomyoma. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4882. doi:10.1158/1538-7445.AM2013-4882