Impact of HER-2 Overexpression/Amplification on the Prognosis of Gastric Cancer Patients Undergoing Resection: A Single-Center Study of 1,036 Patients

Abstract

BACKGROUND Opinions regarding the impact of human epidermal growth factor receptor (HER)-2 overexpression or HER-2 amplification on the prognosis of gastric cancer patients are mixed. The present study attempted to clarify this issue by investigating a large cohort of surgical patients. METHODS We investigated 1,036 gastric cancer patients undergoing curative-intent resection. Their surgical specimens were evaluated for HER-2 expression by immunohistochemistry (IHC), and those with HER-2 expression levels of 2+ were additionally subjected to fluorescence in situ hybridization (FISH). Data on demographic and clinicopathological features and relevant prognostic factors in these patients were analyzed. RESULTS HER-2 positivity was noted in 64 (6.1%) of 1,036 gastric cancer patients, including 46 patients whose HER-2 expression level was 3+ on IHC and 18 patients whose FISH results were positive. On univariate analysis, HER-2 positivity was more often associated with differentiated histology, intestinal type, and negative resection margins, whereas only differentiated histology was independently associated with HER-2 positivity in a logistic regression model. For stage I-IV gastric cancer, HER-2 was not a prognostic factor. In a subpopulation study, although HER-2 positivity emerged as a favorable prognostic factor for stage III-IV gastric cancer on univariate analysis, it failed to be an independent prognostic factor after multivariate adjustment. CONCLUSIONS The prevalence of HER-2 positivity, determined using standardized assays and scoring criteria in a large cohort of gastric cancer patients after resection, was 6.1%. HER-2 positivity was phenotypically associated with differentiated histology. HER-2 is not an independent prognostic factor for gastric cancer.