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.

Figure 1.

Evaluation of HER-2 overexpression and HER-2 amplification. (A): HER-2 overexpression evaluated by IHC in well-differentiated intestinal-type gastric carcinoma (IHC score, 3+). (B): FISH targeting HER-2 in gastric cancer specimen. Red-labeled probes targeting HER-2 and green-labeled probes targeting chromosome 17 centromere are stained with DAPI (FISH +). Abbreviations: DAPI, 4′,6′-diamidino-2-phenylindole dihydrochloride; FISH, fluorescence in situ hybridization; HER-2, human epidermal growth factor receptor 2; IHC, immunohistochemistry.