Assessment of EGFR and ERBB2 (HER2) in Gastric and Gastroesophageal Carcinomas: EGFR Amplification is Associated With a Worse Prognosis in Early Stage and Well to Moderately Differentiated Carcinoma

Abstract

Epidermal growth factor receptor 1 (EGFR) and erb-b2 receptor tyrosine kinase 2 (ERBB2/HER2) are frequently dysregulated in human cancers. We analyzed EGFR and ERBB2 status in 105 gastric and gastroesophageal junction carcinoma and their clinicopathologic features. For EGFR, 92 (88%) tumors were scored as 0, 2 (2%) as 1+, 7 (7%) as 2+, and 4 (3%) as 3+ by immunohistochemistry (IHC) and 4 (4%) tumors showed EGFR amplification by fluorescence in situ hybridization (FISH). For ERBB2, 90 (86%) tumors were scored as 0, 4 (4%) as 1+, 6 (6%) as 2+, and 5 (5%) as 3+ by IHC and 12 (12%) showed ERBB2 amplification by FISH. The concordance rate between IHC and FISH of EGFR was 98.1% (P<0.001) and of ERBB2 was 93.3% (P<0.001). Most tumors with ERBB2 amplification were tubular adenocarcinoma (N=11, P=0.02) and Lauren intestinal type (N=12, P=0.016). There was no statistically significant difference between EGFR amplification and tumor classification. EGFR amplification had significant impact on overall survival in certain subgroups: early stages (stages I and II) (P<0.001), well to moderately differentiated tumors (P=0.001), and fewer regional lymph node metastasis (pN1) (P=0.001). ERBB2 status had little predictive value on overall survival. In conclusion, this study showed ERBB2 amplification was significantly observed in tubular adenocarcinoma and Lauren intestinal-type carcinoma. The IHC scoring criteria for ERBB2 can be applied to EGFR. EGFR amplification had associated with poor prognosis in early, well to moderately differentiated carcinoma.