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Gynaecological cancers

2172 - Prognostic relevance of immune-related gene expression signatures (irGES) in patients (pts) with ovarian clear cell carcinomas (OCCC)

Date

09 Sep 2017

Session

Gynaecological cancers

Presenters

Valerie Heong

Citation

Annals of Oncology (2017) 28 (suppl_5): v330-v354. 10.1093/annonc/mdx372

Authors

V. Heong1, D. Lim2, T.Z. Tan3, J. Ye3, Y.W. Lim1, S.E. Lim1, J. Ng4, A. Ilancheran4, J. Loh4, R. Soong3, D. Tan1, R. Huang3

Author affiliations

  • 1 Haematology-oncology, National University Hospital, 119074 - Singapore/SG
  • 2 Pathology, National University Hospital, 119074 - Singapore/SG
  • 3 Cancer Science Institute, National University Singapore, 119074 - Singapore/SG
  • 4 Gynecology Oncology, National University Hospital, 119074 - Singapore/SG
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Resources

Abstract 2172

Background

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.

Methods

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).

Results

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 

Conclusions

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

not applicable

Legal entity responsible for the study

Institute Review Board SIngapore

Funding

None

Disclosure

All authors have declared no conflicts of interest.

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