HER2 expression/amplification: Frequency, clinicopathologic features, and prognosis in 713 patients with esophageal adenocarcinoma (EAC).

Abstract

4012 Background: HER2 testing in EAC is now routine after regulatory approval of trastuzumab in advanced gastroesophageal cancer. But in EAC the frequency of HER2 expression (exp), its correlation with gene amplification (amp), clinicopathologic features, and prognosis are unknown. Methods: We examined HER2 exp (HercepTest, immunohistochemistry [IHC]) in resection specimens (n = 713) from our institution (1980–97). No patient had neoadjuvant therapy. HER2 amp (fluorescent in situ hybridization [FISH]) was assessed in all 172 IHC2+ and in an unselected subset of IHC3+/0-1+ cases. Per gastric cancer guidelines, amp+ was defined as HER2/CEP17 ratio ≥2.0; and HER2-positive (pos) status (using IHC and FISH) was defined as IHC3+, or IHC2+ plus amp+. Cox models were used. Results: Tumors were 65% T3-4 and 71% node-positive. By location, 35% were esophageal and 65% gastroesophageal junction [GEJ]/cardia. Frequency of HER2 exp and its correlation with amp are shown (Table). In IHC2+ cases, 15% (25/172) were amp+. Using IHC and FISH data, the HER2-posrate was 17% (119/713). HER2 exp and amp had high agreement (κ = .89 [95% CI 0.75 – 1.0]). HER2-pos frequency was higher in esophageal versus GEJ/cardia subsites (21% vs. 15%; p=.03). HER2-pos (vs. -negative) status was associated with lower grade (p<.0001), absence of signet rings (p=.009), lower T stage (p=.03), and fewer malignant nodes (p=.006). HER2-pos status was associated with favorable overall (hazard ratio [HR] 0.75 [0.59 – 0.97]; p=.02) and disease-specific survival (HR 0.79 [0.62 – 1.01]; p=.06), but not after covariate adjustment (p=.18). Conclusions: In the largest study of HER2 in EAC to date, we found HER2-pos frequency was 17%, with high agreement between exp and amp. In IHC2+ tumors, 15% were amp+. In contrast to breast cancer, HER2-pos status in EAC is not associated with adverse survival. The equivalent frequency of HER2 exp/amp in nonmetastatic EAC with that in metastatic gastric cancer may inform future evaluation of trastuzumab therapy in EAC. n = 713 3+ High n = 94 2+ Medium n = 172 0 – 1+ Absent – low n = 447 HER2 protein exp 13% 24% 63% HER2 Amp tested 18 172 20 HER2 Amp+ 94% (17) 15% (25) 5% (1)