Non-incidental coamplification of Myc and ERBB2, and Myc and EGFR, in gastric adenocarcinomas
Non-incidental coamplification of Myc and ERBB2, and Myc and EGFR, in gastric adenocarcinomas
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DOI：
10.1038/modpathol.3800777
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发表时间：
2007-06-01
期刊：
影响因子：
7.5
通讯作者：
Ooi, Akishi
中科院分区：
文献类型：
--
作者：
Mitsui, Fumihiko;Dobashi, Yoh;Ooi, Akishi
本研究旨在评估Myc蛋白过表达和基因扩增的频率，并确定Myc基因扩增的机制，特别是关于其与ERBB 2或EGFR在胃腺癌中可能的共扩增。通过对300例经福尔马林固定和石蜡包埋的胃腺癌进行免疫组化分析，在47例（16%）肿瘤中发现了MYC的核过表达。荧光原位杂交（FISH）分析显示，在47个蛋白质过表达的肿瘤中，有9个（19%）具有高水平Myc扩增的癌细胞，而在122个没有蛋白质过表达的肿瘤中，只有7个（6%）显示高水平Myc基因扩增。这种Myc扩增与阳性核蛋白过表达显著相关。分别在6例和4例病例中发现的ERBB 2或EGFR与Myc的共扩增被认为是非偶然的，因为这些频率显著高于在总检查病例中观察到的个体频率（ERBB 2：7%; EGFR：4%）。这三个基因的高水平的基因扩增，如通过FISH所可视化的，可以大致分为两种典型的类型，即，“多个分散的信号”和“大的聚集的信号”。使用双色FISH，共扩增的Myc和ERBB 2，或Myc和EGFR，在单个细胞核内的扩增类型和拷贝数的各种组合的共存，可以确定在所有9例，其中包括一个同步的“多分散型”共扩增的Myc和ERBB 2观察。在三种肿瘤中，发现了ERBB 2和EGFR的共扩增;然而，ERBB 2和EGFR扩增的细胞群是分开的，相互排斥的。我们认为Myc和ERBB 2或EGFR的非偶然共扩增是通过易位和随后的重排发生的。
This study was conducted to assess the frequencies of protein overexpression and gene amplification of Myc and to identify the mechanisms of Myc gene amplification, especially with regards to its possible coamplification with ERBB2 or EGFR in gastric adenocarcinomas. By immunohistochemical analysis of a total of 300 formalin-fixed and paraffin-embedded gastric adenocarcinomas, the nuclear overexpression of MYC was found in 47 tumors (16%). A fluorescence in situ hybridization (FISH) analysis revealed that nine (19%) of the 47 tumors with protein overexpression had cancer cells with high levels of Myc amplification, whereas only seven (6%) of the 122 tumors without protein overexpression showed high-level Myc gene amplification. Such Myc amplification was significantly correlated with positive nuclear protein overexpression. The coamplification of ERBB2 or EGFR with Myc that was found in six and four cases, respectively, is believed to be non-incidental because those frequencies were significantly higher than the individual frequencies observed for the total examined cases (ERBB2: 7%; EGFR: 4%). The high levels of gene amplification of these three genes, as visualized by FISH, could be broadly classified into two typical types, namely, 'multiple scattered signals' and 'large clustered signals'. Using two-color FISH, the coexistence of coamplified Myc and ERBB2, or Myc and EGFR, within single nuclei in various combinations of amplification types and copy numbers, could be ascertained in all nine cases, including one in which the synchronous 'multiple scattered type' coamplification of Myc and ERBB2 was observed. In three tumors, coamplification of ERBB2 and EGFR was found; however, ERBB2- and EGFR-amplified cell populations were separate and mutually exclusive. We propose that the non-incidental coamplification of Myc and either ERBB2 or EGFR occurred through translocation and subsequent rearrangement.