652P - EGFR and AKT1 overexpression are mutually exclusive and associated with a poor survival in resected adenocarcinomas of the stomach and gastro-esoph...

Date 29 September 2014
Event ESMO 2014
Session Poster Display session
Topics Oesophageal Cancer
Gastric Cancer
Pathology/Molecular Biology
Translational Research
Presenter Iacopo Petrini
Citation Annals of Oncology (2014) 25 (suppl_4): iv210-iv253. 10.1093/annonc/mdu334
Authors I. Petrini1, M. Lencioni1, E. Vasile1, L. Begliuomini1, L. Ginocchi1, C. Caparello1, G. Musettini1, C. Vivaldi1, S. Caponi1, A. Proietti2, G. Fontanini3, G. Naccarato2, V. Nardini3, S. Santi4, A. Falcone5
  • 1Oncologia, Trapianti E Nuove Tecnologie In Medicina, Polo Oncologico - Azienda Ospedaliero-Universitaria Pisana - Istituto Toscano Tumori, 56126 - Pisa/IT
  • 2Surgical Pathology, Pisa University Hospital, Pisa/IT
  • 3Pathology, Azienda Ospedaliera Universitaria Pisana, Pisa/IT
  • 4Department Of Gastroenterology, Esophageal Surgery Unit, Tuscany Regional Referral Center for the Diagnosis and Treatment of Esophageal Disease, Pisa, Italy, Pisa/IT
  • 5Dept. Of Oncology-presidio Ospedaliero, Azienda Ospedaliero Univesitaria S.Chiara, IT-56100 - Pisa/IT

Abstract

Aim

Trastuzumab is effective for the treatment of advanced gastric cancers with HER2 amplification. Beside HER2 amplification, several molecular targets are under evaluation in metastatic gastric tumors. We evaluated the role of HER2, EGFR, MET, AKT1 and phospho-mTOR expression in resected stage II-III adenocarcinomas.

Methods

92 patients with resected stomach (63%) or gastro-esophageal adenocarcinomas (27%) were evaluated using immunohistochemistry. Antibodies anti- HER2, EGFR, MET, AKT1 and phospho-mTOR were used for immunostaining of formalin-fixed paraffin-embedded tumors' slides. Using FISH, HER2 amplification was evaluated in cases with a 2+ staining.

Results

EGFR overexpression (11%) was a poor prognostic factor for overall survival (3-year OS: 47% vs 77%; Log-Rank p = 0.033). MET overexpression (36%) was associated with a trend for a worse survival (3-year OS: 65% vs 77%; Log-Rank p = 0.084). HER2 amplification/overexpression and mTOR hyper-phosphorylation were observed in 13% and 48% of tumors, respectively. AKT1 overexpression (8%) was mutually exclusive with that of EGFR and together defined a subgroup of tumors with a poor prognosis (3-year OS: 52% vs. 79%, Log-Rank p = 0.005).

Conclusions

EGFR was confirmed a poor prognostic factor in resected gastric cancers. We firstly describe a mutually exclusive overexpression of EGFR and AKT1 with potential prognostic implications, suggesting the relevance of this pathway for the growth of gastric cancers.

Disclosure

All authors have declared no conflicts of interest.