Comparison of HER2 gene amplification (AMP) in primary esophageal and gastroesophageal junction adenocarcinomas (EAC) and their metastatic regional lymph nodes (MLNs).

Abstract

4059 Background: The status of HER2 AMP in primary EACs compared to their MLNs is unknown. This is clinically important since selection of patients for HER2-targeted therapy is usually based on HER2 analysis in primary tumors. Here, we report the largest HER2 evaluation of MLNs in EACs to date. Methods: Resected primary tumors and MLNs (209 patients) were tested for HER2 AMP (fluorescence in situ hybridization) and protein expression (immunohistochemistry; IHC 0, 1+, 2+, 3+). Primaries were designated AMP-positive (pos) or -negative (neg) using standard criteria (HER2/CEP17 ≥ 2 in > 5% tumor cells). HER2AMP status in primaries and MLNs were compared (Wilcoxon, Fisher’s). Results: HER2 by AMP vs IHC within individual MLNs (726 MLNs; median 3 MLNs per patient) were 92% concordant (P < .0001). HER2 AMP status was concordant in primaries vs MLNs in 89% (186/209) of patients (Table). Yet among AMP-neg primaries, 7% (10/146) had at least 1 AMP-pos MLN. Importantly, among AMP-neg primaries (n = 146), those with a small AMP subpopulation (ie, < 1% tumor cells) were more likely than uniformly AMP-neg primaries to have an AMP-pos MLN (33% vs 4%; P = .001). Among AMP-pos primaries, those with non-uniform AMP (ie, 6% - 49% tumor cells) were more likely than uniform AMP primaries (ie, ≥ 50% tumor cells) to have entirely AMP-neg MLNs. Across the whole cohort, among patients with at least 1 AMP-pos MLN, an average of 95% of MLNs (standard deviation 17%) was AMP-pos. Conclusions: HER2 status was generally concordant between primary EACs and MLNs. But the strength of concordance diminished significantly among primaries with a small HER2-amplified subpopulation, where a considerably higher rate of HER2-amplified nodal metastases was observed compared to uniformly non-amplified primaries. These novel data suggest that testing MLNs in this subgroup may identify new candidates for HER2-targeted therapy. Primary tumor MLNs All MLNs are AMP-neg Any MLN is AMP-pos P AMP-neg n = 146 Uniform neg n = 131 96% (126) 4% (5) 0.001 Small AMP subpopulation n = 15 67% (10) 33% (5) AMP-pos n = 63 Uniform pos n = 54 17% (9) 83% (45) 0.078 Non-uniform pos n = 9 44% (4) 56% (5)