Frequent overexpression of multiple ErbB receptors by head and neck squamous cell carcinoma contrasts with rare antibody immunity in patients
Frequent overexpression of multiple ErbB receptors by head and neck squamous cell carcinoma contrasts with rare antibody immunity in patients
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DOI：
10.1002/path.1642
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发表时间：
2004-11-01
影响因子：
7.3
通讯作者：
Muraro, R
中科院分区：
文献类型：
--
作者：
Bei, R;Budillon, A;Muraro, R
为了阐明 ErbB 受体在人头颈鳞状细胞癌 (HNSCC) 中的作用，通过免疫组织化学方法，与邻近正常粘膜的 38 例癌症中的表皮生长因子受体 (EGFR)、ErbB2、ErbB3 和 ErbB4 以及 EGF 和生腱蛋白一起研究了表达异常和亚细胞定位。 24例。尽管肿瘤特异性过度表达影响每种 ErbB 受体（EGFR 47%、ErbB2 29%、ErbB3 21%、ErbB4 26%），但 EGFR 异常最为普遍。后者以及同一肿瘤中两种以上 ErbB 受体（始终包括 EGFR）的过度表达与转移性疾病相关。 ErbB 产物在细胞膜和细胞质中被特异性检测到。相比之下，ErbB4 在 7 种癌症和肿瘤衍生细胞系中独特地定位于细胞核，表明调节膜内蛋白水解作用，导致 HNSCC 中 ErbB4 核易位。原型配体 EGF 或低亲和力基质激活剂生腱蛋白的表达与 EGFR 过度表达显着相关，这意味着 EGFR 慢性激活。在大多数这些病例中，额外的 ErbB 受体同时过度表达表明受体异二聚体反复参与。尽管 ErbB 受体经常发生变化，但自体 ErbB 血清抗体很少，38 名肿瘤患者中只有 1 名患者表现出 ErbB2 特异性免疫反应。基于几种已知免疫抑制分子的上调，ErbB 特异性抗体的缺乏与 HNSCC 中天然肿瘤特异性免疫反应的减弱是一致的。版权所有 (C) 2004 大不列颠及爱尔兰病理学会。约翰·威利儿子有限公司出版
In an effort to elucidate the role of ErbB receptors in human head and neck squamous cell carcinoma (HNSCC), expression abnormalities and subcellular localization of epidermal growth factor receptor (EGFR), ErbB2, ErbB3, and ErbB4 were investigated along with EGF and tenascin by immunohistochemistry in 38 carcinomas as compared to adjacent normal mucosa of 24 cases. Although tumour-specific overexpression affected each ErbB receptor (EGFR 47%, ErbB2 29%, ErbB3 21%, ErbB4 26%), EGFR abnormalities were most prevalent. The latter, and overexpression of more than two ErbB receptors in the same tumour, which always included EGFR, correlated with metastatic disease. ErbB products were specifically detected on the cell membrane and in the cytoplasm. In contrast, ErbB4 was uniquely localized to the nucleus in 7 carcinomas and a tumour-derived cell line, indicating a role for regulated intramembrane proteolysis resulting in nuclear ErbB4 translocation in HNSCC. Expression of prototype ligand EGF or low-affinity stromal activator tenascin correlated significantly with EGFR overexpression, implying chronic EGFR activation. Simultaneous overexpression of additional ErbB receptors in most of these cases suggested recurrent involvement of receptor heterodimers. In spite of frequent ErbB receptor alterations, autologous ErbB serum antibodies were rare, with only I of 38 tumour patients exhibiting an ErbB2-specific immune response. Based on upregulation of several known immunosuppressive molecules, scarcity of ErbB-specific antibodies is consistent with attenuation of natural tumour-specific immune responses in HNSCC. Copyright (C) 2004 Pathological Society of Great Britain and Ireland. Published by John Wiley Sons, Ltd.