Evidence of high incidence of EGFRvIII expression and coexpression with EGFR in human invasive breast cancer by laser capture microdissection and immunohistochemical analysis
Evidence of high incidence of EGFRvIII expression and coexpression with EGFR in human invasive breast cancer by laser capture microdissection and immunohistochemical analysis
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DOI：
10.1002/ijc.10224
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发表时间：
2002-03-20
影响因子：
6.4
通讯作者：
Tang, CK
中科院分区：
文献类型：
--
作者：
Ge, H;Gong, XQ;Tang, CK
EGFRvIII 首次在人类胶质母细胞瘤中报道。随后的报告表明 EGFRvIII 蛋白经常在其他几种人类癌症中检测到，但在正常组织中却没有检测到。我们之前的研究表明，EGFRvIII 可以在体外和体内诱导配体依赖性非致瘤细胞系向配体非依赖性恶性表型细胞的转化。在 MCF-7 细胞系中转染 EGFRvIII 导致集落形成增加 3 倍，并显着增强裸鼠的致瘤性（p < 0.001）。 EGFRvIII 还可以诱导 ErbB-2 磷酸化。然而，EGFRvIII 转录物在人类乳腺癌中的存在和意义尚未报道。在我们的研究中，我们利用激光捕获显微切割 (LCM)/RT-PCR 捕获纯乳腺癌细胞，检测到 EGFRvIII mRNA 的存在，并揭示了人类原发性浸润性乳腺癌中 EGFRvIII 转录物的高发生率 (67.8%)。此外，57.1%的浸润性乳腺癌在同一肿瘤中同时表达EGFRwt和EGFRvIII mRNA。正常乳腺组织中未检测到 EGFRvIII mRNA。通过免疫组织化学分析对同一样本组中的 EGFRwt 和 EGFRvIII 蛋白水平进行评估进一步证实了 LCM/RT-PCR 的发现。我们的研究首次提供了人类浸润性乳腺癌组织中 EGFRvIII 和 EGFRwt 共表达高发生率的直接证据。 EGFRvIII 在侵袭性人类乳腺癌中的独特特征和高患病率以及在正常乳腺中的阴性表达可能表明其在乳腺癌发生中的重要作用，并使其成为在不中断正常 EGFR 信号传导的情况下治疗乳腺癌的理想潜在靶点。 (C) 2002 Wiley-Liss, Inc.
EGFRvIII was first reported in human glioblastomas. Subsequent reports indicated EGFRvIII protein to be frequently detected in several other human cancers, but not in normal tissues. Our previous studies suggested that EGFRvIII could induce a transformation from ligand-dependent non-tumorigenic cell line to ligand-independent malignant phenotype cells in vitro and in vivo. Transfection of EGFRvIII in MCF-7 cell line resulted in a 3-fold increase in colony formation and significantly enhanced tumorigenicity in nude mice, (p < 0.001). EGFRvIII could also induce ErbB-2 phosphorylation. The existence and significance of EGFRvIII transcript in human breast cancer, however, was not reported. In our study, we detected the presence of EGFRvIII mRNA and revealed a high incidence (67.8%) of EGFRvIII transcript in human primary invasive breast cancer by utilizing laser capture microdissection (LCM)/RT-PCR to capture pure breast cancer cells. In addition, 57.1% of the infiltrating breast carcinomas expressed both EGFRwt and EGFRvIII mRNA in the same tumor. There is no detectable EGFRvIII mRNA in normal breast tissue. Evaluation of the EGFRwt and EGFRvIII protein levels in the same sample sets by immunohistochemical analysis further confirmed the LCM/RT-PCR finding. Our study provides first direct evidence of high incidence of co-expression of EGFRvIII and EGFRwt in human invasive breast cancer tissue. The unique characteristics and high prevalence of EGFRvIII in invasive human breast cancer as well as negative expression in normal breast may suggest its important role in breast carcinogenesis and make it an ideally potential target for treatment of breast cancer without interrupting normal EGFR signaling. (C) 2002 Wiley-Liss, Inc.