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Poster display session

5083 - Genomic instability is associated with increased immune infiltration and PDL1 expression in epithelial ovarian cancer

Date

09 Sep 2017

Session

Poster display session

Topics

Translational Research;  Ovarian Cancer

Presenters

Alexandra Leary

Citation

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

Authors

A. Leary1, C. Genestie2, Y. Boursin3, J. Adam4, A. Leformal-Ensarguex5, S. Gouy6, P. Morice6, E. Bentivegna6, P. Pautier7, J. Michels7, B. Job3, M. Deloger3, S. Mesnage1, A. Auguste5

Author affiliations

  • 1 Gynaecologic Oncology, Gustave Roussy Cancer Center, INSERM U981, and Groupe d'Investigateurs Nationaux pour l'Etude des Cancers Ovariens (GINECO), 94800 - Villejuif/FR
  • 2 Department Of Pathology, Institut Gustave Roussy, 94800 - Villejuif/FR
  • 3 Bigr-bioinformatic, Gustave Roussy, Villejuif/FR
  • 4 Pathology, Institut Gustave Roussy, 94800 - Villejuif/FR
  • 5 U981 Inserm, Gustave Roussy, Villejuif/FR
  • 6 Department Of Surgery, Gustave Roussy, Villejuif/FR
  • 7 Medical Oncology, Gustave Roussy Institut de Cancérologie, 94805 - Villejuif/FR
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Resources

Abstract 5083

Background

High mutation load secondary to mutagenic exposures such as smoking or to mutations in mismatch DNA repair genes has been associated with increased tumor immune infiltration and response to immune therapies. Ovarian cancers (OC) demonstrate low mutation load, but high degree of genomic instability (GI) attributable to frequent defects in the homologous recombination DNA repair pathway. We sought to investigate whether GI predicted increased infiltration by tumor infiltrating lymphocytes (TILs) and PDL1 expression in OC.

Methods

TILs were evaluated on FFPE OC samples and scored as percentage of stromal area. PDL1 expression was quantified as percent positive immune cells. GI was measured as the number of copy number alterations >15Mb by Oncoscan SNParray on DNA from the same FFPE samples and high GI score (GIS) defined as > median. Correlations were evaluated using a Spearman rank and differences by Mann-Whitney.

Results

66 tumor samples were evaluable for both GIS and immune infiltration. GIS and TILs showed significant variability ranging from 0 to 64 (median=28) and from 5 to 90% (median=20%) for GIS and TILs, respectively. GIS was significantly higher among high grade serous or endometrioid OC than among low grade tumors (GIS=29 vs 5; p 

Conclusions

High genomic instability correlated with increased tumor infiltrating lymphocytes and PDL1 expression. Whether GIS could provide a simple and predictive biomarker for immune therapies in OC should be investigated.

Clinical trial identification

Legal entity responsible for the study

LEARY Alexandra

Funding

INCa (Institut national du cancer)

Disclosure

All authors have declared no conflicts of interest.

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