Little is known about the immune microenvironment of OCCCs and its impact on outcomes. We studied the expression of a panel of immune response genes in OCCC to identify the presence and prognostic relevance of irGES in these tumours.
Immune response gene profiling was performed on 84 FFPE OCCC samples with matched clinical outcomes, collected between 2003 – 2016, using the nanoString nCounter PanCancer Immune Profiling Panel. Unsupervised hierarchical clustering analysis was performed and each sample underwent analysis for protein levels of PD-1, PD-L1, MMR and ARID1A via immunohistochemistry (IHC).
Total of 74/84 samples were successfully profiled. Median age at diagnosis was 53 yrs. 41 (55.4%) were stage 1, 7 (9.5%) stage 2, 24 (32.4%) Stage3, 2 (2.7%) stage 4. 64/74 (86.5%) of pts received adjuvant chemotherapy post debulking surgery with 38% recurrence rate (median PFS 27 months (m)). Median follow up was 36m. Based on irGES, 4 distinct molecular subgroups of OCCCs were identified. G1 was hallmarked by high NK cell markers/PD-1 expression, G2 by increased CTLA-4/PD-L1 expression, G3 by adhesion cell markers, and G4 by increased levels of pro - angiogenic genes. G1 was observed to have significantly poorer PFS (median PFS 20m vs 68m, p= 0.011) and a trend towards poorer OS when compared with G2/3/4 (median OS 38.8m vs undefined, p = 0.0501). G4 carried the best prognosis (median PFS 108m vs 26m, p= 0.0515; median OS undefined, p= 0.0726). This difference in OS and PFS was reflected in stage 1 pts (p
OCCCs are heterogeneous and can be classified into 4 molecular subgroups based on their irGES profiles with distinct clinicopathological characteristics and prognostic outcomes. If validated in larger datasets, these signatures may serve to inform a clinical trial.
Clinical trial identification
Legal entity responsible for the study
Institute Review Board SIngapore
All authors have declared no conflicts of interest.