[687] Prevalence and Prognostic Significance of HER2 Amplification in Adenocarcinoma of the Esophagus and GE Junction.

Oana Radu, Katie Nason, Jon Davison. UPMC, Pittsburgh, PA

Background: The ToGA trial showed that trastuzumab (a monoclonal antibody targeting HER2) with conventional chemotherapy improves survival in advanced gastric or GE junction (GEJ) adenocarcinoma, underscoring the therapeutic importance of HER2 amplification and overexpression. There are conflicting reports of the prognostic significance of HER2 amplification in esophageal or GEJ adenocarcinoma (EAC). In this study we assess the association of HER2 amplification with pathologic features and survival in a large series of EAC treated by esophagectomy.
Design: 82 patients who underwent esophagectomy from 2000-2004 for EAC were prospectively evaluated for HER2 amplification. Dual-color FISH using a HER2 region probe and a chromosome 17 centromeric probe (CEP17) (Pathvysion, Abbott Molecular) was performed on paraffin sections of the resected tumor (N=79) or pre-operative biopsy (N=3). Pathologic, clinical and survival data was obtained for all patients by review of the medical record.
Results: Twenty-seven of 82 (32.9%) patients had HER2 amplification using a HER2/CEP17 ratio cutoff of 2.2. The HER2/CEP17 range for amplified cases was 2.2 – 42.6. The distribution of these results is summarized in Table 1.

HER2 FISH Results

HER2/CEP17 Ratio	Number of Cases (%)
> 4.0	10 (12.2)
2.2-4.0	17 (20.7)
1.8-2.2	4 (4.9)
1.5-1.8	10 (12.2)
< 1.5	41 (50.0)
Total	82 (100)

There were no significant differences between HER2 amplified and non-amplified cases with respect to age, gender, TNM stage, tumor grade, perineural and angiolymphatic invasion, intestinal metaplasia, columnar dysplasia, or margin status. The median recurrence free survival was 18.3 mo for HER2 amplified cases and 24.9 mo for non-amplified cases, but the survival functions were not significantly different (Kaplan-Meier, log rank test). HER2 amplification had no significant effect on overall survival (Kaplan-Meier, log rank test).
Conclusions: The frequency of HER2 amplification in EAC in this series (32.9%) is consistent with what has been reported for EAC (15-54%). In contrast to other reports, we saw no association with tumor grade, nor other conventionally reported pathologic variables. We also failed to observe any significant adverse effect on survival in univariate analysis, consistent with the larger of two previous studies. The number of cases may be insufficient to detect a small effect. HER2 protein overexpression may be a better prognostic marker based on comparison to the literature.
Category: Gastrointestinal

Monday, February 28, 2011 1:00 PM

Poster Session II # 96, Monday Afternoon