Zhang Xiu Li, Yang Yun Sheng, Xu Dong Ping, Qu Jian Hui, Guo Ming Zhou, Gong Yan, Huang Jin
Department of Gastroenterology and Hepatology, Chinese PLA General Hospital, 28 Fuxing Road, Beijing, 100853, China.
World J Surg. 2009 Oct;33(10):2112-8. doi: 10.1007/s00268-009-0142-z.
Owing to the special importance of the HER family in tumorigenesis, the downstream signaling pathways and effectors have become the key molecules in the strategy of carcinoma-targeted therapy. Recent evidence that HER3 is responsible for tumor resistance to therapeutic agents targeting EGFR or HER2/neu, along with the new findings that HER3 is involved in the process of dedifferentiation of gastric cancer (GC) have highlighted the critical role of HER3 in cancer research. HER3 is becoming a new targeted molecule in cancer treatment. Here, we comparatively investigated the expression of HER2/neu and HER3 in gastric cancer of two pathologic types (intestinal type and diffuse type) using immunohistochemistry (IHC) and analyzed the correlation between overexpression of HER2 and HER3 and clinicopathologic parameters.
An IHC study for HER2 and HER3 was performed on 102 formalin-fixed, paraffin-embedded specimens of GC-60 intestinal and 42 diffuse types. The correlation between overexpression of HER2 and HER3 and clinicopathologic parameters was statistically analyzed.
In the GC group, overexpression of HER2 and HER3 was detected in 19 (18.6%) and 14 (13.7%) of 102 GC patients, respectively. In a nontumorous group of 102 specimens, 5 were HER2-positive (4.9%) (18.6% vs. 4.9%, p < 0.01), and 2 were HER3-positive (2.0%) (13.7% vs. 2.0%, p < 0.01). No co-overexpression of HER2 and HER3 was observed. The intestinal type of GC exhibited a higher rate of HER2 overexpression than did the diffuse type (26.7% vs. 7.1%, p < 0.05), whereas the diffuse type of GC exhibited a significantly higher rate of HER3 overexpression than did the intestinal type (26.2% vs. 5.0%, p < 0.01). The overexpression rates of HER2 and HER3 in phase III-IV (TNM stage) disease were significantly higher than that in phase I-II disease (24.0% vs. 7.7%, p < 0.05 and 22.0% vs. 5.8%, p < 0.05, respectively). HER2 and HER3 overexpression was also correlated with a significantly worse survival (p = 0.046 and 0.024, respectively).
The selective overexpression of HER2 and HER3 in the two histologic types of gastric cancer is strongly associated with a poor prognosis. Being an important member of the HER family, HER3 may become another candidate for molecular-targeted therapy in gastric cancer, especially for the diffuse histologic type.
由于HER家族在肿瘤发生过程中具有特殊重要性，其下游信号通路和效应分子已成为靶向治疗癌症策略中的关键分子。最近有证据表明HER3与肿瘤对靶向EGFR或HER2/neu治疗药物的耐药性有关，同时还有新发现表明HER3参与胃癌（GC）的去分化过程，这些都凸显了HER3在癌症研究中的关键作用。HER3正成为癌症治疗中的一个新的靶向分子。在此，我们采用免疫组织化学（IHC）方法比较研究了两种病理类型（肠型和弥漫型）胃癌中HER2/neu和HER3的表达情况，并分析了HER2和HER3过表达与临床病理参数之间的相关性。
对102例福尔马林固定、石蜡包埋的GC标本（60例肠型和42例弥漫型）进行HER2和HER3的IHC研究。对HER2和HER3过表达与临床病理参数之间的相关性进行统计学分析。
在GC组中，102例GC患者中分别有19例（18.6%）和14例（13.7%）检测到HER2和HER3过表达。在102例非肿瘤标本组中，5例HER2阳性（4.9%）（18.6%对4.9%，p<0.01），2例HER3阳性（2.0%）（13.7%对2.0%，p<0.01）。未观察到HER2和HER3共同过表达。肠型GC的HER2过表达率高于弥漫型（26.7%对7.1%，p<0.05），而弥漫型GC的HER3过表达率显著高于肠型（26.2%对5.0%，p<0.01）。III-IV期（TNM分期）疾病中HER2和HER3的过表达率显著高于I-II期疾病（分别为24.0%对7.7%，p<0.05和22.0%对5.8%，p<0.05）。HER2和HER3过表达也与生存率显著降低相关（分别为p=0.046和0.024）。
两种组织学类型胃癌中HER2和HER3的选择性过表达与预后不良密切相关。作为HER家族的重要成员，HER3可能成为胃癌分子靶向治疗的另一个候选靶点，尤其是对于弥漫型组织学类型的胃癌。
