He Xiao Xiao, Ding Li, Lin Yuan, Shu Man, Wen Jian Ming, Xue Ling
Department of Pathology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.
J Clin Pathol. 2015 May;68(5):374-80. doi: 10.1136/jclinpath-2014-202657. Epub 2015 Mar 2.
Despite significant improvements in targeted therapies for patients with advanced gastric cancer (GC), the prognosis of those patients remains poor. This study explores the expression and clinicopathological significance of human epidermal growth factor receptor 2, 3 and 4 (HER2, HER3, HER4) in GC, in order to find more prognostic biomarkers of GC and putative targets of therapy.
Immunohistochemistry was performed for HER2, HER3 and HER4 in 498 patients with GC using tissue microarray. Correlations between the receptor expression and clinicopathological features, as well as prognosis of the patients were statistically analysed.
The high expression rates of HER2, HER3 and HER4 proteins in the patients were 8.6% (43/498), 20.7% (103/498) and 13.3% (66/498), respectively. High expression of HER2 and HER3 was correlated with proximal GC of the cardia (p<0.05). High expression of HER3 was associated with the tumour depth, tumour node metastasis (TNM) stage and lymph node metastasis (p<0.05). High expression of HER4 was associated with TNM stage (p<0.05) only. According to a regression model, high expression of HER3 was significantly associated with patients' poor survival (p=0.004). High expression rates of HER2, HER3 and HER4 were correlated with each other, but they were all associated merely with histologically intestinal-type adenocarcinoma of GC (p<0.05).
HER3 is correlated with the malignant biological behaviour of GC. Expression of HER3 is a significant predictor of poor survival in GC. Therefore, the development of HER3-targeted agents may provide new possibilities in the treatment of GC.
尽管晚期胃癌（GC）患者的靶向治疗有了显著改善，但这些患者的预后仍然很差。本研究探讨人表皮生长因子受体2、3和4（HER2、HER3、HER4）在GC中的表达及其临床病理意义，以寻找更多GC的预后生物标志物和潜在治疗靶点。
使用组织芯片对498例GC患者进行HER2、HER3和HER4的免疫组织化学检测。对受体表达与临床病理特征以及患者预后之间的相关性进行统计学分析。
患者中HER2、HER3和HER4蛋白的高表达率分别为8.6%（43/498）、20.7%（103/498）和13.3%（66/498）。HER2和HER3的高表达与贲门近端GC相关（p<0.05）。HER3的高表达与肿瘤深度、肿瘤淋巴结转移（TNM）分期和淋巴结转移相关（p<0.05）。HER4的高表达仅与TNM分期相关（p<0.05）。根据回归模型，HER3的高表达与患者的不良生存显著相关（p=0.004）。HER2、HER3和HER4的高表达率相互相关，但它们都仅与GC的组织学肠型腺癌相关（p<0.05）。
HER3与GC的恶性生物学行为相关。HER3的表达是GC患者不良生存的重要预测指标。因此，开发针对HER3的药物可能为GC的治疗提供新的可能性。
