Metaplastic breast carcinomas exhibit EGFR, but not HER2, gene amplification and overexpression: immunohistochemical and chromogenic in situ hybridization analysis.
Metaplastic breast carcinomas exhibit EGFR, but not HER2, gene amplification and overexpression: immunohistochemical and chromogenic in situ hybridization analysis.
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DOI：
10.1186/bcr1341
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发表时间：
2005
期刊：
影响因子：
--
通讯作者：
Schmitt FC
中科院分区：
文献类型：
--
作者：
Reis-Filho JS;Milanezi F;Carvalho S;Simpson PT;Steele D;Savage K;Lambros MB;Pereira EM;Nesland JM;Lakhani SR;Schmitt FC
化生性乳腺癌构成了一组异质性肿瘤，占所有浸润性乳腺癌的不到1%。大约70-80%的化生性乳腺癌过表达表皮生长因子受体（EGFR）。人表皮生长因子受体（HER）2和EGFR在过去几年中在医学文献中引起了广泛关注，这是由于针对HER 2的人源化单克隆抗体和针对EGFR的细胞外配体结合结构域或细胞内酪氨酸激酶结构域的疗法已被证明在治疗某些类型的人类癌症中是成功的。我们调查了一系列化生性乳腺癌中是否存在HER 2和EGFR过表达，并评估了基因扩增。使用EGFR的单克隆抗体（31 G7）和HER 2的两种抗体（Herceptest和CB 11）对25例化生性乳腺癌进行免疫化学分析，并使用Herceptest评分系统进行评分。使用Zymed Spot-Light EGFR和HER 2扩增探针通过显色原位杂交评价基因扩增。在40×和63×物镜下通过明场显微镜评价结果。19例（76%）化生性乳腺癌显示EGFR过度表达，其中7例（37%）检测到EGFR扩增（定义为大基因簇或>50%肿瘤细胞中>5个信号/核）：3例鳞状分化癌和4例梭形细胞癌。1例病例显示HER 2过度表达为2+级（>10%的细胞具有弱至中度完全膜染色），但未检测到HER 2基因扩增。化生性乳腺癌经常过度表达EGFR，这与三分之一的病例中EGFR基因扩增有关。我们的研究结果表明，一些化生性乳腺癌患者可能受益于新的治疗靶向EGFR。因为大多数化生性乳腺癌过度表达EGFR而没有基因扩增，所以需要进一步研究评估EGFR激活突变。
Metaplastic breast carcinomas constitute a heterogeneous group of neoplasms, accounting for less than 1% of all invasive mammary carcinomas. Approximately 70–80% of metaplastic breast carcinomas overexpress the epidermal growth factor receptor (EGFR). Human epidermal growth factor receptor (HER)2 and EGFR have attracted much attention in the medical literature over the past few years owing to the fact that humanized monoclonal antibodies against HER2 and therapies directed against the extracellular ligand-binding domain or the intracellular tyrosine kinase domain of EGFR have proven successful in treating certain types of human cancer. We investigated whether HER2 and EGFR overexpression was present and evaluated gene amplification in a series of metaplastic breast carcinomas. Twenty-five metaplastic breast carcinomas were immunohistochemically analyzed using a monoclonal antibody (31G7) for EGFR and two antibodies for HER2 (Herceptest and CB11) and scored using the Herceptest scoring system. Gene amplification was evaluated by chromogenic in situ hybridization using Zymed Spot-Light EGFR and HER2 amplification probe. The results were evaluated by bright field microscopy under 40× and 63× objective lenses. Nineteen (76%) metaplastic breast carcinomas exhibited EGFR ovexpression, and among these EGFR amplification (defined either by large gene clusters or >5 signals/nucleus in >50% of neoplastic cells) was detected in seven cases (37%): three carcinomas with squamous differentiation and four spindle cell carcinomas. One case exhibited HER2 overexpression of grade 2+ (>10% of cells with weak to moderate complete membrane staining), but HER2 gene amplification was not detected. Metaplastic breast carcinomas frequently overexpressed EGFR, which was associated with EGFR gene amplification in one-third of cases. Our findings suggest that some patients with metaplastic breast carcinomas might benefit from novel therapies targeting EGFR. Because most metaplastic breast carcinomas overexpress EGFR without gene amplification, further studies to evaluate EGFR activating mutations are warranted.
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影响因子：
158.5
作者：
Lynch, TJ;Bell, DW;Haber, DA
通讯作者：
Haber, DA
影响因子：
3.5
作者：
Popnikolov, NK;Ayala, AG;Gatalica, Z
通讯作者：
Gatalica, Z
影响因子：
45.3
作者：
DiGiovanna, MP;Stern, DF;Thor, AD
通讯作者：
Thor, AD
影响因子：
--
作者：
Corzo, C;Tusquets, I;Solé, F
通讯作者：
Solé, F
影响因子：
--
作者：
Marquez, A;Wu, R;Shi, ZR
通讯作者：
Shi, ZR