640P - Molecular portrait of resected gastric cancer (RGC) with next generation sequencing (NGS) according to a clinical biological risk model considering...

Date 29 September 2014
Event ESMO 2014
Session Poster Display session
Topics Gastric Cancer
Pathology/Molecular Biology
Translational Research
Presenter Emilio Bria
Citation Annals of Oncology (2014) 25 (suppl_4): iv210-iv253. 10.1093/annonc/mdu334
Authors E. Bria1, M. Fassan2, S. Pilotto1, G. De Manzoni3, S. Kinspergher1, I. Sperduti4, U. Peretti1, M. Simbolo2, P. Capelli5, A. Tomezzoli6, C. Luchini5, A. Mafficini2, G. Turri2, G. Tortora7, A. Scarpa8
  • 1Medical Oncology, Azienda Ospedaliera Universitaria Integrata Verona-"Borgo Roma", 37134 - Verona/IT
  • 2Pathology, ARC-NET Applied Research on Cancer Center, 37134 - Verona/IT
  • 3Surgical Oncology, Azienda Ospedaliera Universitaria Integrata Verona-"Borgo Roma", 37129 - Verona/IT
  • 4Biostatistics, Regina Elena National Cancer Institute, 00144 - Roma/IT
  • 5Pathology, Azienda Ospedaliera Universitaria Integrata Verona-"Borgo Roma", 37134 - Verona/IT
  • 6Pathology And Diagnostics, University of Verona, Verona/IT
  • 7Oncologia Medica, Azienda Ospedaliera Universitaria Integrata Verona-"Borgo Roma", 37134 - Verona/IT
  • 8Patologia E Diagnostica, Anatomia Patologica, Azienda Ospedaliera Universitaria Integrata Verona-Borgo Roma, 37134 - Verona/IT

Abstract

Aim

FHIT, APC and HER-2 have recently shown to powerfully complement clinical factors to significantly discriminate prognosis for RGC. Additional genetic alterations potentially driving both outcome and treatment may be concurrently screened with NGS multigene analysis.

Methods

On the bases of a internally validated model (Bria E, Ann Oncol 2013), tumor blocks from 114 intestinal-histology patients at Good (2-yrs Cancer Specific Survival 89.7% and Overall Survival 84.8%) and Poor prognosis (CSS 7.3% and OS <1%) were analyzed for mutations in 50 cancer-associated genes using multiplex PCR amplification of DNA from microdissected paraffin samples and the Ion AmpliSeq Cancer Panel (Life Technologies).

Results

Forty-two patients displayed to be Good and Poor prognostic performers at both CSS and OS; 34 patients (80.9%) were evaluable for NGS analysis. Patients' characteristics: Good (N = 21; male/female: 13/8; grading: 1-2/3: 9/12; median F.U.: 70.8; median CSS not reached; 10-yrs CSS: 58.9%; median OS: 115.0 [95% CI 33-197]; 10-yrs OS: 45.9%); Poor (N = 13, male/female: 9/4; grading: 1-2/3: 6/7; median F.U.: 10.8; median CSS and OS 7.0 [95% CI 2-12]; 1-yr CSS/OS: 7.7%). A significant difference between Good and Poor patients was found for median age (p = 0.021), resected nodes (p = 0.018), and positive node-ratio (p<0.0001). Seventeen (Good/Poor: 14/3), 11 (Good/Poor: 5/6) and 6 (Good/Poor: 2/4) RGC contained multiple, single or none gene alteration, respectively. The most frequently mutated genes (>3) follows:

Good Poor p-value
KRAS 8 (38.1%) 1 (7.7%) 0.11
PI3KCA 8 (38.1%) 2 (15.4%) 0.25
TP53 6 (28.6%) 3 (23.1%) 0.99
MET 2 (9.5%) 1 (7.7%) 0.99
SMAD4 1 (4.8%) 2 (15.4%) 0.54
STK11 1 (4.8%) 2 (15.4%) 0.54

ATM, CDKN2A, EGFR, ERBB2, FBXW7, SMARCB1, were mutated in 2 cases, while FGFR3, IDH1, JAK3, KIT, NOTCH1, NRAS, PTEN, in 1.

Conclusions

These exploratory findings suggest that NGS technologies with formalin-fixed and paraffin embedded tissues may potentially help to drive future customized therapies for RGC, and deserve to be prospectively tested together with clinical parameters in the context of larger samples.

Disclosure

All authors have declared no conflicts of interest.