Prognostic significance of Human epidermal growth factor receptor-2 expression in patients with resectable gastric adenocarcinoma

Abstract

Background The purpose of this study was to investigate the correlation between human epidermal growth factor receptor 2 (HER2) overexpression and clinicopathologic factors and overall survival rate in patients who underwent curative gastrectomy for gastric adenocarcinoma. Methods Among patients who underwent curative gastrectomy for gastric adenocarcinoma at Inje University Paik Hospital from January 2012 to December 2015, 782 patients underwent an immunohistochemical analysis to evaluate HER2 expression levels. Clinicopathologic records that were collected from a gastric cancer database were retrospectively reviewed to identify clinicopathologic factors and survival rates of the patients. Results HER2 overexpression was detected in 166 patients (21.2%). There was a statistically significant correlation between HER2 expression level and sex ( p = 0.013), histologic differentiation ( p < 0.001), Lauren classification ( p < 0.001), and T pathologic stage ( p = 0.022). There were no statistically significant relationships between HER2 expression level and overall 5-year survival rate ( p = 0.775) and overall 5-year survival rate of gastric adenocarcinoma classified according to the TNM stage (stage I: p = 0.756, stage II: p = 0.571, stage III: p = 0.704). The HER2 expression level was not affected by the overall 5-year survival rate in the uni- and multivariate analyses. Conclusions In this study, the HER2 overexpression rate in gastric adenocarcinoma was 21.2% and was observed in well- and moderately differentiated types according to histologic differentiation, intestinal type according to the Lauren classification, male, and low T stage. There was no correlation between HER2 expression level and overall 5-year survival rate, and HER2 expression level was not associated with independent prognostic factors.

The clinical and prognostic significance of HER2 and Ki67 expression in 2062 Chinese patients with resectable gastric cancer: a retrospective study

“…16 Moreover, the OS rates was compared between 1521 low HER2 expression patients and 190 high HER2 expression patients and the results did not indicate a signi cant survival difference for 1-year OS (60.6% vs 61.5%), 3-year OS (51.3% vs 53.8%) or 5-year OS (26.6% vs 27.6%), which was consistent with the analysis in 810 Korean GC patients. 17 However, two other studies demonstrated that HER2 overexpression is associated with poor survival outcomes in 100 Iranian patients and 1148 Japanese cases with GC. 18,19 The reasons for the inconsistent results could be partly attributed to the heterogeneity of HER2 expression among different ethnic populations or the effects of sample size.…”

Identification of Potential Genes in Her2+ Breast Cancer by Co-expression Network Analysis

“…ERBB2, generally named Her2, is amplified or overexpressed in 20-30% of invasive breast carcinomas [7]. Moreover, amplification and overexpression of Her2 gene has also been detected in ovarian and gastric cancer [8][9][10]. Her2 integrates firmly to other epidermal growth factor receptor family members to assemble a heterodimer, which reinforce kinase-mediated activation of downstream signaling pathways, such as PI3K/AKT activation and RET signaling, so as to facilitate the increment and metastasis of cancer cells [11].…”

“…The gradient method was employed to weigh the connection strength between each pair of nodes and assess the independence and average degree connectivity of the assorted modules with different power values (range [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20]. In this work, the value whose independence degree was greater than 0.8 for the first time was seems as the appropriate power value (β) to ensure a scale-free network.…”

Identification of New Key Genes in Breast Cancer by Co-expression Network Analysis

“…ERBB2, commonly referred to as HER2, encodes a member of the epidermal growth factor receptor family of receptor tyrosine kinases, it is amplified and/or overexpressed in 20-30% of invasive breast carcinomas [13]. Amplification and/or overexpression of this gene have also been reported in many other cancers including ovarian and gastric cancer [14][15][16]. ERBB2 binds tightly to other ligand-bound EGF receptor family members to form a heterodimer, stabilizing ligand binding and enhancing kinase-mediated activation of downstream signaling pathways, such as PI3K/AKT activation and RET signaling [17].…”