Early HER2 dysregulation in gastric and oesophageal carcinogenesis
Early HER2 dysregulation in gastric and oesophageal carcinogenesis
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DOI：
10.1111/j.1365-2559.2012.04272.x
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发表时间：
2012-11-01
期刊：
影响因子：
6.4
通讯作者：
Rugge, Massimo
中科院分区：
文献类型：
--
作者：
Fassan, Matteo;Mastracci, Luca;Rugge, Massimo
目的：探讨人表皮生长因子受体2(HER2)在肠型胃癌(GC)和Barretts腺癌(BAC)发生过程中的组织学表型[化生、上皮内瘤变(IEN，即异型增生)和腺癌]中的表达情况。方法与结果：对275例胃和食道组织标本(代表胃癌和Barretts癌发生过程中的全部表型变化)进行了研究。应用两种免疫组织化学(IHC)方法，使用抗体4B5和CB11来评估HER2状态。对同一组织标本进行双色银染色质原位杂交。在食道和胃组织中，HER2过表达率从低度恶性到高度恶性到腺癌均显著升高(P<；0.001)，两种免疫组化染色结果一致(一致性95%；k=0.78；P<；0.001)。瘤内异质性在GC和BAC中均有记录(使用两种IHC方案)。HER2扩增率(SISH)随去分化程度的增加而显著增加(P<；0.001)。无论是天然的还是化生的粘膜样本(取自胃或食道)都没有显示出HER2扩增。HER2扩增与蛋白过度表达有很好的一致性(两种IHC方案：SISH/4B5一致性97.8%，k=0.89，P<；0.001；SISH/CB11一致性97.8%，k=0.91，P<；0.001)。结论：胃(肠型)和Barretts癌的发生与HER2异常(扩增和蛋白过度表达)均有早期参与。
Aims: To explore human epidermal growth factor receptor 2 (HER2) status in the histological phenotypes [metaplasia, intraepithelial neoplasia (IEN, i.e. dysplasia), and adenocarcinoma] involved in the morphogenesis of both intestinal-type gastric cancer (GC) and Barretts adenocarcinoma (BAc).Methods and results: A consecutive series of 275 samples of stomach and oesophagus tissue (representing the whole spectrum of the phenotypic changes involved in gastric and Barretts carcinogenesis) was studied. HER2 status was assessed by applying two immunohistochemistry (IHC) protocols, using the antibodies 4B5 and CB11. Dual-colour silver chromogenic in-situ hybridization (SISH) was also performed on the same tissue samples. In both oesophageal and gastric samples, the rate of HER2 overexpression rose significantly from low-grade to high-grade IEN to adenocarcinoma (P < 0.001), with the two IHC protocols showing consistent staining (consistency 95%; k = 0.78; P < 0.001). Intratumour heterogeneity was documented in both GC and BAc (using both IHC protocols). The rate of HER2 amplification (using SISH) increased significantly along with IEN dedifferentiation (P < 0.001). Neither native nor metaplastic mucosa samples (obtained from either stomach or oesophagus) ever showed HER2 amplification. There was excellent agreement between HER2 amplification and protein overexpression (both IHC protocols: SISH/4B5consistency 97.8%, k = 0.89, P < 0.001; SISH/CB11consistency 97.8%, k = 0.91, P < 0.001).Conclusions: There is early involvement of HER2 dysregulation (amplification and protein overexpression) in both gastric (intestinal-type) and Barretts oncogenesis.