Gene dosage PCR and fluorescence in situ hybridization reveal low frequency of egfr amplifications despite protein overexpression in invasive breast carcinoma
Gene dosage PCR and fluorescence in situ hybridization reveal low frequency of egfr amplifications despite protein overexpression in invasive breast carcinoma
复制标题
DOI：
10.1038/labinvest.3700077
复制
发表时间：
2004-05-01
影响因子：
5
通讯作者：
Buerger, H
中科院分区：
文献类型：
--
作者：
Kersting, C;Tidow, N;Buerger, H
本研究的目的是评估侵袭性乳腺癌中 egfr 全基因和 CA 内含子重复扩增的频率，作为表皮生长因子受体 (EGFR) 蛋白过度表达的机制。通过组织微阵列，通过免疫组织化学和 FISH 分别评估了 222 例浸润性乳腺癌的蛋白质过表达和全基因扩增。通过 Taqman RT-PCR 评估第一个内含子 CA 重复扩增。通过 FISH 和 RT-PCR，分别有 4.7% 和 6.3% 的病例显示全基因和第一个内含子 CA 重复扩增。 RT-PCR 中的扩增剂量在两倍和四倍之间变化。通过免疫组织化学检测，17.3%显示EGFR过度表达。不同方法之间的相关性较低。总共有 2.9% 的病例同时显示全基因扩增和内含子 CA 重复扩增，而 90.3% 的病例两者均为阴性。近20%的免疫组化蛋白过表达病例显示出内含子CA重复扩增，而免疫组化阴性的病例中只有2.2%显示出内含子CA重复扩增。总体而言，13% 的蛋白过度表达病例通过 FISH 显示扩增，而只有 1.6% 的免疫组化阴性病例显示这种扩增。在 EGFR 过度表达的病例中，4 例 (25%) 显示全基因或内含子 CA 重复扩增。总之，egfr 的全基因扩增在浸润性乳腺癌中很少见，并且只能解释约 12.5% 的浸润性乳腺癌病例中蛋白质过度表达。第一个内含子第一个 CA 重复扩增是 EGFR 蛋白过度表达的另一个重要机制，解释了约 18.7% 病例中的蛋白过度表达。然而，由于约 75% 的 EGFR 蛋白过度表达病例缺乏这两种扩增中的任何一种，因此必须考虑其他表达调节机制。
The aim of this study was to assess the frequency of egfr whole gene and CA intron repeat amplification in invasive breast cancer as a mechanism for epidermal growth factor receptor (EGFR) protein overexpression. By means of tissue microarrays, protein overexpression and whole gene amplification were assessed in 222 cases of invasive breast cancer by immunohistochemistry and FISH, respectively. First intron CA repeat amplification was assessed by Taqman RT-PCR. With FISH and RT-PCR, 4.7 and 6.3% of cases showed whole gene and first intron CA repeat amplification, respectively. Amplification dosage varied between two- and four-fold in RT-PCR. By immunohistochemistry, 17.3% showed EGFR overexpression. There was a low correlation between the different methods. In all, 2.9% of cases showed both whole gene amplification and intron CA repeat amplification, and 90.3% of cases were negative for both. Nearly 20% of cases with immunohistochemical protein overexpression showed intron CA repeat amplification, and only 2.2% of cases that were negative on immunohistochemistry showed such amplification. In all, 13% of cases with protein overexpression showed amplification by FISH, and only 1.6% of cases that were negative on immunohistochemistry showed such amplification. Of the cases with EGFR overexpression, 4 (25%) showed either whole gene or intron CA repeat amplification. In conclusion, whole gene amplifications of egfr are rare in invasive breast cancer and explain protein overexpression in only about 12.5% of invasive breast cancer cases. First intron first CA repeat amplification is another important mechanism for EGFR protein overexpression, explaining protein overexpression in about 18.7% of cases. However, since about 75% of cases with EGFR protein overexpression lack either of these amplifications, other expression regulating mechanisms must be considered.