Makatsoris Thomas, Tsamandas Athanassios C, Strimpakos Alexios, Alexopoulou Zoi, Dionysopoulos Dimitrios, Pervana Stavroula, Konstantara Athina, Papakostas Pavlos, Samantas Epaminontas, Rallis Grigoris, Dimou Anastasios, Pentheroudakis George, Papaparaskeva Kleo, Psyrri Amanda, Kalogeras Konstantine T, Syrigos Kostas, Scopa Chrisoula D, Fountzilas George
Division of Oncology, Department of Medicine, University Hospital, University of Patras Medical School, Patras, Greece
Department of Pathology, University Hospital, University of Patras Medical School, Patras, Greece.
Anticancer Res. 2016 Apr;36(4):1581-90.
Gastric cancer is a relatively common malignancy. Recently, the presence of the human epidermal growth factor receptor 2 (HER2) was identified as a molecular target in a proportion of patients who benefited from the addition of appropriate anti-HER2 treatments. Our study explored the clinical and prognostic role of known HER family members, human epidermal growth factor receptor 1 (EGFR or HER1), HER2, HER3 and HER4.
Formalin-fixed paraffin-embedded (FFPE) tumor tissue samples from 249 gastric cancer patients were studied by immunohistochemistry for protein expression of EGFR, HER2, HER3 and HER4.
Of the 249 evaluable patients, 32 did not have complete data of treatment details and/or follow-up and were excluded from the survival analyses. Of the 217 patients with complete treatment and follow-up data, 178 were operated and treated for early disease (group 1), while 39 for advanced disease (group 2). The frequency of positive EGFR, HER2, HER3 and HER4 protein expression in all patients was 17.5%, 11.8%, 14.8% and 32.9%, respectively. There were no differences in protein expression of any of the markers between the two groups. There were, however, statistically significant associations between HER4 and all other HER family members, as well as between HER2 and HER3 expression. Of note, EGFR-positive membranous protein expression was significantly associated with the presence of lymphovascular invasion (p=0.027) and HER3 and HER4 negative cytoplasmic protein expression with well/moderately-differentiated tumors (p=0.030 and p=0.014, respectively). None of the HER family members were of prognostic value for OS in univariate analysis.
The present study confirmed the known protein expression frequencies of HER family members in gastric cancer in a Greek population. Several associations were observed among the HER family members and between clinicopathological characteristics and HER family members. Further research is needed on their exact prognostic role, as well as their therapeutic targeting.
胃癌是一种相对常见的恶性肿瘤。最近，人类表皮生长因子受体2（HER2）的存在被确定为一部分患者的分子靶点，这些患者从添加适当的抗HER2治疗中获益。我们的研究探讨了已知HER家族成员，即人类表皮生长因子受体1（EGFR或HER1）、HER2、HER3和HER4的临床和预后作用。
采用免疫组织化学方法研究了249例胃癌患者福尔马林固定石蜡包埋（FFPE）肿瘤组织样本中EGFR、HER2、HER3和HER4的蛋白表达情况。
在249例可评估患者中，32例没有完整的治疗细节和/或随访数据，被排除在生存分析之外。在217例有完整治疗和随访数据的患者中，178例接受了早期疾病的手术治疗（第1组），39例接受了晚期疾病的手术治疗（第2组）。所有患者中EGFR、HER2、HER3和HER4蛋白表达阳性的频率分别为17.5%、11.8%、14.8%和32.9%。两组之间任何标志物的蛋白表达均无差异。然而，HER4与所有其他HER家族成员之间以及HER2和HER3表达之间存在统计学显著关联。值得注意的是，EGFR阳性膜蛋白表达与淋巴管侵犯显著相关（p=0.027），HER3和HER4阴性细胞质蛋白表达与高/中分化肿瘤显著相关（分别为p=0.030和p=0.014）。在单变量分析中，没有一个HER家族成员对总生存期具有预后价值。
本研究证实了希腊人群中胃癌HER家族成员已知的蛋白表达频率。在HER家族成员之间以及临床病理特征与HER家族成员之间观察到了几种关联。需要进一步研究它们的确切预后作用以及治疗靶向性。
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