Oops, you're using an old version of your browser so some of the features on this page may not be displaying properly.

MINIMAL Requirements: Google Chrome 24+Mozilla Firefox 20+Internet Explorer 11Opera 15–18Apple Safari 7SeaMonkey 2.15-2.23

Poster Display session 2

5123 - TP53 Hotspot mutations as immunoreactive neoantigens define a signature with differential survival outcomes in advanced ovarian cancer

Date

29 Sep 2019

Session

Poster Display session 2

Topics

Tumour Site

Ovarian Cancer

Presenters

Marica Garziera

Citation

Annals of Oncology (2019) 30 (suppl_5): v403-v434. 10.1093/annonc/mdz250

Authors

M. Garziera1, E. Cecchin1, J. Polesel2, V. Canzonieri3, R. Sorio4, S. Gagno1, S. Scalone4, R. Roncato1, E. De Mattia1, E. Poletto5, G. Giorda6

Author affiliations

  • 1 Experimental And Clinical Pharmacology Unit, Centro di Riferimento Oncologico (CRO), IRCCS, 33081 - Aviano/IT
  • 2 Unit Of Cancer Epidemiology, Centro di Riferimento Oncologico (CRO), IRCCS, 33081 - Aviano/IT
  • 3 Pathology Unit, Centro Di Riferimento Oncologico (cro), Irccs, 33081 Aviano, Italy, Centro di Riferimento Oncologico (CRO), IRCCS, 33081 - Aviano/IT
  • 4 Department Of Medical Oncology, Centro di Riferimento Oncologico - CRO, 33081 - Aviano/IT
  • 5 Department Of Oncology, Azienda Sanitaria Universitaria Integrata di Udine - Ospedale Santa Maria della Misericordia, 33100 - Udine/IT
  • 6 Gynaecological Oncology Unit, Centro di Riferimento Oncologico (CRO), IRCCS, 33081 - Aviano/IT

Resources

Login to get immediate access to this content.

If you do not have an ESMO account, please create one for free.

Abstract 5123

Background

Hotspot mutations (HSM) in TP53 (R175, Y220, G245; R248, R273) have been recognized as potential immunoreactive neoantigens able to achieve intratumoral T cell responses in advanced ovarian cancer, particularly in high-grade serous ovarian cancer (HGSOC). The purpose of this study was to assess if HSM, Non-HSM (missense non-HSM) and Other (INDELs, stop gained, splice site) somatic mutations in TP53, confer differential survival outcomes. Presence of circulating p53-autoantibodies (p53-AAbs) was also tested and correlated with TP53 mutation spectra.

Methods

A series of 83 patients (71 HGSOC) with advanced (III-IV stage, G2-3) ovarian cancer, treated with primary debulking surgery and platinum-based therapy, were retrospectively enrolled. Characterization of TP53 mutations in chemo-naïve tumours was performed with a targeted next-generation sequencing approach. An ELISA kit was used to detect p53-AAbs. Platinum-free interval (PFI), progression-free survival (PFS) and Overall survival (OS) were compared using Kaplan-Meier, Log-rank test and Cox proportional hazard models (adjusted for age, stage, serous subtype, residual tumour).

Results

Somatic mutations in TP53 were found in 74.7% of patients; among them, 71% was -p53-AAbs and 29% was +p53-AAbs. The repertoire of TP53 mutations was significantly different according to p53-AAbs (p = 0.005), with prevalence of Other mutations (50%) in patients -p53-AAbs. In multivariate analysis (WT as the ref. category), patients with: i) Non-HSM mutations had reduced PFI (p = 0.026), PFS (p = 0.014) and OS (p = 0.048); ii) Other mutations had reduced PFI (p = 0.002) and PFS (p = 0.007), but not OS (p = 0.062); iii) HSM mutations were not associated with PFI (p = 0.605), PFS (p = 0.681) and OS (p = 0.437).

Conclusions

Molecular profile of chemo-naïve tumours in advanced ovarian cancer showed different outcomes coupled to specific TP53 signatures. A more aggressive mutational profile in TP53 was observed in patients without p53-AAbs. Non-synonymous mutated neoantigens arised from tumour clones, appear to be critical to identify patients best suited to immunotherapy. Further investigations in the tumour microenvironment are needed to confirm these preliminary findings.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Giorgio Giorda.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

This site uses cookies. Some of these cookies are essential, while others help us improve your experience by providing insights into how the site is being used.

For more detailed information on the cookies we use, please check our Privacy Policy.

Customise settings
  • Necessary cookies enable core functionality. The website cannot function properly without these cookies, and you can only disable them by changing your browser preferences.