Human epidermal growth factor receptor-2 gene amplification in gastric cancer using tissue microarray technology

Abstract

To assess human epidermal growth factor receptor-2 (HER2)-status in gastric cancer and matched lymph node metastases by immunohistochemistry (IHC) and chromogenic in situ hybridization (CISH). 120 cases of primary gastric carcinomas and 45 matched lymph node metastases from patients with full clinicopathological features were mounted onto multiple-punch and single-punch tissue microarrays, respectively, and examined for HER2 overexpression and gene amplification by IHC and CISH. Twenty-four tumors (20%) expressed HER2 immunohistochemically. An IHC score of ≥ 2+ was observed in 20 tumors (16.6%). HER2 amplification was detected by CISH in 19 tumors (15.8%) and in their matched lymph node metastases. A high concordance rate was found between HER2 positivity (as detected by IHC) and HER2 gene amplification (as detected by CISH), since 19 of the 20 IHC positive cases were amplified (95%). All amplified cases had 2+ or 3+ IHC results. Amplification was associated with intestinal phenotype (P < 0.05). No association with grading, staging or survival was found. In gastric cancer, HER2 amplification is the main mechanism for HER2 protein overexpression and is preserved in lymph node metastases.