Correlation of HER2 and PTEN status with clinical outcome in esophageal (E), gastric (G), and gastroesophageal junction (GEJ) adenocarcinomas (ACs).

Abstract

4066 Background: The determination of HER2 status is now critical for the management of E, G and GEJ AC's. Loss of expression of the PTEN tumor suppressor protein is considered to be a significant predictor of resistance to trastuzumab in the treatment of breast cancer. Methods: HER2 status was determined on 141 FFPE invasive AC's [13 E, 52 G and 76 GEJ] both by FISH (Abbott Molecular PathVysion) and IHC (Ventana Pathway and Dako HercepTeston a subset of cases) using the US FDA slide scoring criteria. PTEN expression was determined by IHC (rabbit mAB, Cell Signaling) using an automated method (Ventana) and semi-quantitative slide scoring. H&E slides were reviewed for all 44 endoscopic biopsies and 97 surgical resections included in the study, tumors were graded and staged according to the AJCC manual (7th ed). Results: While HER2 amplification/overexpression was markedly heterogeneous in both biopsy and resection specimens, extremely high correlation of FISH and IHC for HER2 status (p<0.001) was observed when the overexpressed foci were targeted for FISH examination. All (100%) IHC 2+ and 3+ cases were FISH+. Of 118 IHC 0 and 1+ cases, only 1 case (<1%) was discordant (FISH+). No cases featured HER2+ in situ carcinoma that did not also have HER2+ invasive carcinoma. HER2 status correlated with tumor site (26% GEJ vs. 8% E vs. 6% G, p=0.006), but not with grade, stage or survival. PTEN expression was lost in 70% of cases overall, and 83% (p=0.12) of HER2+ cases. PTEN loss was associated with advanced stage (p=0.005) and showed a trend toward correlation with shortened survival (p=0.09) in HER2+ cases. Conclusions: Unlike previous reports from the ToGA trial, in this series of 141 ACs there was extremely high correlation of FISH and IHC for determining HER2 status in E, G and GEJ tumors. HER2 is amplified/overexpressed in E, G and GEJ ACs, but not associated with aggressive disease in this study. PTEN expression was lost in the majority of HER2+ cases and correlated with aggressive disease. Further study of the association of PTEN with HER2 status and the interaction of PTEN with response to trastuzumab for the treatment of E, G and GEJ AC's appears warranted.