Evaluation of HER-2 gene status in gastric carcinoma using immunohistochemistry, fluorescence in situ hybridization, and real-time quantitative polymerase chain reaction
Evaluation of HER-2 gene status in gastric carcinoma using immunohistochemistry, fluorescence in situ hybridization, and real-time quantitative polymerase chain reaction
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DOI：
10.1016/j.humpath.2007.02.005
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发表时间：
2007-09-01
期刊：
影响因子：
3.3
通讯作者：
Kim, Woo Ho
中科院分区：
文献类型：
--
作者：
Kim, Min A.;Jung, Eun Ji;Kim, Woo Ho
在包括胃癌在内的各种实体瘤中观察到 HER-2 基因扩增和 HER-2 蛋白过度表达。自新治疗药物曲妥珠单抗开发以来，HER-2基因扩增引起了研究关注。在这里，我们使用免疫组织化学（IHC）、荧光原位杂交（FISH）和实时定量聚合酶链反应（q-PCR）评估了248例胃癌手术切除组织中的HER-2状态，并比较了结果。此外，我们还比较了 HER-2 基因扩增和蛋白质过表达的临床病理特征。 248例中，IHC显示56例（22.6%）HER-2过表达（2+或3+），FISH显示19例（7.7%）HER-2基因扩增。 192 例 IHC 阴性（0 或 1+）的病例中有 4 例（2.1%）显示 FISH 扩增，而 56 例 HER-2 蛋白过表达的病例中有 15 例（26.8%）显示 FISH 扩增 HER-2。 IHC 和 FISH 结果之间的相关性具有统计学显着性 (P < .001)。 HER-2 蛋白过表达和 HER-2 基因扩增常见于根据世界卫生组织分类 (P < .001) 组织学分化良好或中等的病例以及根据 Lauren 分类 (P < .001) 为肠型的病例。实时 q-PCR 结果显示，以 FISH 结果为标准，计算出的 HER-2/GAPDH 比值在扩增病例中较高，敏感性为 100.0%，特异性为 96.9%。发现通过 FISH 和实时 q-PCR 测量的 HER-2 表达以及通过 IHC 测量的 HER-2 蛋白在确定胃癌中 HER-2 状态方面高度一致。 (c) 2007 Elsevier Inc. 保留所有权利。
HER-2 gene amplification and the overexpression of HER-2 protein have been observed in various solid tumors, including gastric carcinomas. HER-2 gene amplification has attracted research attention since the development of the new therapeutic agent trastuzumab. Here, we evaluated HER-2 status in the surgically resected tissues of 248 gastric carcinoma cases using immunohistochemistry (IHC), fluorescence in situ hybridization (FISH), and real-time quantitative polymerase chain reaction (q-PCR) and compared the results. In addition, we compared clinicopathologic characteristics with the presence of HER-2 gene amplification and with protein overexpression. Among the 248 cases, 56 (22.6%) cases showed HER-2 overexpression (2+ or 3+) by IHC and 19 cases (7.7%) showed HER-2 gene amplification by FISH. Four (2.1%) of the 192 cases negative (0 or 1+) by IHC showed amplification by FISH, whereas 15 (26.8%) of the 56 cases with HER-2 protein overexpression showed HER-2 amplification by FISH. The correlation between IHC and FISH results was statistically significant (P < .001). HER-2 protein overexpression and HER-2 gene amplification were common in cases with a well- or moderately differentiated histology according to the World Health Organization classification (P < .001) and in cases of intestinal type by the Lauren classification (P < .001). Real-time q-PCR results showed that calculated HER-2/GAPDH ratios were higher in amplified cases with 100.0% sensitivity and 96.9% specificity using FISH results as the standard. Measurements of HER-2 expression by FISH and real-time q-PCR and of HER-2 protein by IHC were found to be highly concordant at determining HER-2 status in gastric carcinoma. (c) 2007 Elsevier Inc. All rights reserved.