Immunogenicity of clear cell ovarian cancer: Association with ARID1A loss, microsatellite instability and endometriosis.

5514 Background: Studies of immune checkpoint inhibitors (e.g., anti-PD-1/PD-L1 antibodies) in ovarian cancer have demonstrated isolated responses in tumors with clear cell histology. In order to assess the immunogenicity of clear cell ovarian cancer (CCOC), we evaluated the presence of CD3+, CD8+ and CD4+ tumor-infiltrating lymphocytes (TILs) and the expression of PD-1 and PD-L1 in CCOCs as compared to high grade serous ovarian cancers (HGSOCs). These findings were also correlated with presence of ARID1A loss, microsatellite instability (MSI) and endometriosis in CCOCs. Methods: In this pilot study, 30 CCOCs were evaluated and compared with 53 HGSOCs. Immunohistochemistry (IHC) was performed for CD3, CD4, CD8, PD-1 and PD-L1 using standard protocols. PD-1 and PD-L1 were evaluated in both intraepithelial and peritumoral immune cells; PD-L1 was also evaluated in tumor cells. MSI status and ARID1A/BAF250a loss were determined via IHC. Results: Of the 30 CCOCs, 3 (10%) exhibited MSI, 8 (26.6%) exhibited loss of ARID1A, and 22 (73.3%) were associated with personal history and/or histologic evidence of endometriosis. CCOCs with MSI had a higher number of CD3+ TILs (mean 52.33 vs 33, two-tailed p=0.3) and higher number of PD1+TILs (22 vs. 3.56, p<0.001) compared to microsatellite stable (MSS) CCOCs. Furthermore, CCOCs with MSI had a higher number of CD3+ TILs (mean 52.33 vs 36.2, two-tailed p=0.25) and higher number of PD-1+TILs (22 vs. 3.45, p<0.001) compared to HGSOCs. Unlike CCOCs with MSI, there was no significant difference in the number of TILs or PD-1/PD-L1 expression between MSS-CCOCs and HGSOCs. Furthermore, CCOCs with ARID1A loss and CCOCs with endometriosis did not exhibit higher number of TILs or PD-1 or PD-L1 expression than the remaining CCOCs or than HGSOCs. Conclusions: CCOCs with MSI may represent a subset of CCOCs that is more immunogenic and may thus respond favorably to immune checkpoint inhibition. Apart from MSI-CCOCs, we did not detect any difference between CCOCs and HGSOCs in terms of number of TILs and PD-1/PD-L1 expression. Endometriosis and ARID1A loss were not associated with higher number of TILs or PD-1/PD-L1 expression.