High Expression of HER3 Is Associated with a Decreased Survival in Gastric Cancer

Abstract

Background: The role of human epidermal growth factor receptor (HER) 3 and HER4 has been elucidated in gastric cancer. HER1 and HER2 overexpression are regarded as prognostic factors and targets of treatment. The dimerization of the HER family receptors activates downstream signal pathways and promotes tumor progression. This study investigated the positive correlation between HER1and HER4 expression and the prognosis of patients with gastric cancers. Experimental Design: Tumor samples were obtained from gastric adenocarcinomas of 134 patients who underwent a gastrectomy from 1999 to 2002. The expression of each HER was analyzed in the tumor by immunohistochemical staining. Parametric correlations were done between HER expression and the clinicopathologic findings. A multivariate analysis was done with the overall survival. Results: HER3 expression was significantly associated with parameters involved with tumor progression, including the depth of tumor invasion (T 1 versusT 2 -T 4 ; P = 0.000), involved lymph nodes (P = 0.000), distant metastasis (P = 0.008), tumor stage (P = 0.000), and recurrent disease (P = 0.000). HER1was also significantly associated with those factors excluding distant metastasis. A significant relationship was observed between the expression of HER1 and HER3 (P = 0.000). HER3 overexpression was associated with a significantly worse survival (P = 0.0000) and was an independent prognostic factor in the multivariate analysis (hazard ratio, 2.382; 95% confidence interval, 1.009-5.625; P = 0.048). Conclusions: HER3 overexpression is strongly associated with tumor progression and poor prognosis of patients with gastric cancer. It may become a new prognostic factor and a target of treatment.

EGFR family and cMet expression profiles and prognostic significance in esophagogastric adenocarcinoma

“…We demonstrated that the co-expression of HER3 and HER4 at 35% was statistically significant (P=0.019), suggesting that again, HER3 may be acting as a preferred dimerization partner for EGFR family A B members. Indeed, Hayashi and colleagues demonstrated that HER3 membranous expression was also significantly correlated with HER4 expression and associated with tumor progression, higher depth of tumor invasion (T1 vs. T2-T4) involved lymph nodes, distant metastasis tumor stage, recurrences and worse survival (37). We noted overexpression of all EGFR family members in only 17% of the cases.…”

Clinicopathologic factors associated with HER2‐positive gastric cancer and its impact on survival outcomes—A systematic review

“…Early Grabsch et al, 11 Marx et al, 15 Yu et al, 19 Hayashi et al, 22 Potrc et al, 23 Song et al, 30 Pinto-de-Sousa et al, 34 Ghaderi et al 36 [15 Studies (7 studies between 1990 and 1999 not displayed)]…”

“…Not specified Wang et al, 10 Im et al 27 [2 Studies] Marx et al, 15 Yu et al, 19 Hayashi et al, 22 Satiroglu-Tufan et al, 25 Ghaderi et al, 36 Allgayer et al 39 15 Barros-Silva et al, 16 Hayashi et al, 22 Park et al, 24 Tanner et al, 26 Song et al, 30 Garcia et al, 31 Lee et al, 32 Pintode-Sousa et al, 34 Oshima et al 38 [12 Studies (2 studies between 1990 and 1999 not displayed)]…”

Targeting of HER Family Signaling Pathways in Gastric Cancer

“…Intestinal type has predominance of HER2 overexpression over HER3, while diffuse type has increased overexpression of HER3 compared to HER2 [23]. In a study where gastrectomy samples were obtained from 134 patients with gastric adenocarcinomas, HER3 overexpression was significantly correlated with increased depth of tumor invasion, involved lymph nodes, distant metastasis, more advanced tumor stage, and increase in recurrent disease [24]. HER3 overexpression served as a poor prognostic factor in this study.…”