Abstract IA21: Small cell carcinomas of the ovary: Strengths and weaknesses

Abstract

Abstract Small cell carcinoma of the ovary, hypercalcemic type (SCCOHT) is a rare and very aggressive malignancy that occurs mostly in young women. We and others previously described SCCOHT as a SMARCA4-mutated monogenic disease and unraveled other important molecular features, including apparent universal loss of SMARCA2 through epigenetic silencing. Typically, SMARCA4 and SMARCA2 are redundant catalytic subunits of the SWI/SNF complex and loss of either will result in the overexpression of the other. However, SCCOHT is unique in having concomitant loss of both subunits with restoration of either leading to tumor suppression. Nonetheless, despite these advances in understanding the biology of SCCOHT, there are few effective treatment options and survival rates remain poor. In this presentation we will discuss the role of SMARCA4 and SMARCA2 on tumor growth. We will also present therapeutic options to manipulate SWI/SNF complex dependencies. We will present case histories of patients who have had positive responses to targeted therapies. We will also discuss responses to anti-PD1 immunotherapy and characterize the immune landscape of SCCOHT tumors using quantitative immunofluorescence and gene expression profiling. Unexpectedly for a low mutation burden cancer, the majority of the tumors demonstrated PD-L1 expression with strong associated T-cell infiltration. PD-L1 expression can be detected in both tumor and stromal cells, with macrophages being the most abundant PD-L1 positive cells in some tumors. These findings suggest that although SCCOHT are low-mutational-burden tumors, their immunogenic microenvironment that resembles the landscape of tumors that respond well to treatment with PD-1/PD-L1 blockade. Citation Format: Douglas A. Levine. Small cell carcinomas of the ovary: Strengths and weaknesses. [abstract]. In: Proceedings of the AACR Conference: Addressing Critical Questions in Ovarian Cancer Research and Treatment; Oct 1-4, 2017; Pittsburgh, PA. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(15_Suppl):Abstract nr IA21.