4751 - Immune-related gene expression signatures (irGES) in patients (pts) with ovarian clear cell carcinomas (OCCC) – a multicenter analysis

Background

We previously showed that OCCC can be classified into 4 molecular subgroups based on their irGES profiles with distinct clinicopathological characteristics and prognostic outcomes. A combined analysis of samples from 3 independent centres was performed to investigate the prognostic relevance of the irGES profiles in a larger cohort of OCCC patients.

Methods

Immune-related gene profiling was performed on 255 FFPE OCCC samples collected from 3 centres (NUH, Singapore, Saitama, Japan, and Edinburgh, UK) using the nanoString nCounter PanCancer Immune Profiling Panel. Unsupervised hierarchical clustering analysis was performed and correlated with clinical outcome. MMR protein levels were assessed by immunohistochemistry.

Results

Total of 255/264 samples from 3 independent cohorts were successfully profiled. Median age at diagnosis was 57 yrs. 137 (53.7%) were stage 1 (Singapore 46.9%, Saitama 65.8%, Edinburgh 50.6%) with 113 (44.3%) Stages 2-4 (Singapore 47.9%, Saitama 34.2%, Edinburgh 49.4%) and 5 (1.9%) missing data. 68.8%, 80.3% and 80.7% of pts from Singapore, Saitama and Edinburgh respectively, received adjuvant treatment. Median PFS for OCCC pts from Singapore, Saitama and Edinburgh were 27, 29.2 and 31.9 mths, respectively. Median OS were 33.5, 35.1 and 41.6 mths respectively for pts from Singapore, Saitama and Edinburgh. Based on irGES, 4 distinct molecular subgroups of OCCCs were consistently identified and reproducible. The PD-1 high subgroup was observed to have poorer 3 yr OS rate (52% vs 57% vs 73% vs 74%, p = 0.05) and a trend towards poorer 3 year PFS rate (42% vs 58.7% vs 51% vs 65%, p = 0.12) compared to the CTLA4, ProA and AP subgroups respectively. A similar trend was observed when pts were stratified based on stage and whether they received adjuvant treatment. MMR expression levels were noted to be deficient in 6.3% and 5.1% of pts from Singapore and Saitama, respectively and were not significantly associated with any irGES group.

Conclusions

Clinical outcomes, based on irGES profiles, appeared to be similar across Asian and Caucasian OCCC pts. 4 molecular subgroups based on their irGES profiles were consistently identified between 3 independent cohorts with distinct prognostic outcomes.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

NUHS Clinician Scientist Programme-Residency (NCSP-R) Grant NMRC -Centre grant scheme Yong Siew Yoon fellowship grant Clinician Scientist Award (IMAC) CSA-NMRC grant Nicola Murray Foundation.

Disclosure

C. Gourley: Honoraria (self), Advisory / Consultancy: Roche, AstraZeneca, Tesaro, Nucana, Clovis, Foundation One, Sierra Oncology, Cor2Ed; Research grant / Funding (self): AstraZeneca, Novartis, Aprea, Nucana, Tesaro; Licensing / Royalties: PCT/US2012/040805, PCT/GB2013/053202, 1409479.1, 1409476.7 and 1409478.3. D.S. Tan: Honoraria (self): Roche, Bayer, MSD, Genmab, AstraZeneca, Merck Serono, Tessa Therapeutics, Novartis; Research grant / Funding (institution): Bayer, Karyopharm, AstraZeneca. R. Huang: Spouse / Financial dependant: ACT genomics Singapore. All other authors have declared no conflicts of interest.