Presentation description

Synovial Sarcoma (SS) is a rare and aggressive soft-tissue cancer and is the most common Soft-Tissue Sarcoma in children, affecting 1-2 individuals per million in the United States. Its highly metastatic potential is partly due to its propensity for angiogenesis, the growth and development of blood vessels. SS is uniquely characterized by a balanced chromosomal translocation resulting in the fusion of SS18 (a gene which normally encodes a subunit of the BAF chromatin remodeling complexes) to one of three discrete sites within the X chromosome. Each resulting fusion product, SS18::SSX1, SS18::SSX2, or SS18::SSX4, is a potent oncogene. To learn how to treat this rare cancer, our lab created mouse models of SS which conditionally express SS18::SSX1 and precisely mimic the disease in humans. Two potential treatments for SS, Panobinostat (a histone deacetylase inhibitor) and HDM201 (an inhibitor of P53 degradation) were injected peritoneally into mice up to 6 times a week for an average of 24 weeks, either alone or in combination to evaluate the treatment effect on tumor growth. After ~24 weeks, mice were sacrificed and tumors were dissected and embedded in paraffin for further analysis. Using immunohistochemical staining methods, we can identify gene signals associated with cancer growth and degradation. In our analysis, we targeted three genes, Ki67, Cyclin D1, and Caspase 3. Ki67 and Cyclin D1 are both associated with cell proliferation and growth while Caspase 3 is important for apoptosis, or programmed cell death. High levels of Caspase 3 expression with low Cyclin D1 and Ki67 expression would be the desired outcome of this treatment. All sections exhibited varying degrees of proliferation, as well as pro-apoptosis signals. Once the final sections have been stained, our analysis will demonstrate whether the treatment decreases proliferation and increases apoptosis relative to the controls.