Dei Tos A P, Ellis I
Department of Pathology, Regional Hospital of Treviso, Italy.
Eur J Cancer. 2005 Jul;41(10):1383-92. doi: 10.1016/j.ejca.2005.03.018.
Over-expression of the epidermal growth factor receptor (EGFR) in tumours is associated with aggressive disease and poor clinical prognosis. In theory, the EGFR status of a tumour provides an indication of the likelihood of response to EGFR-targeted therapy. However, the clinical data do not support a relationship between EGFR expression and response to EGFR-targeted therapies cetuximab, gefitinib and erlotinib. Recently, patients who appear to lack EGFR expression have been shown to respond to cetuximab. Possible causes for this paradox include false negative results due to a lack of sensitivity in the detection system, heterogeneity of EGFR expression within the tumour and specific mutations that mediate response to the tyrosine kinase inhibitors. Immunohistochemistry is the most reliable assay for EGFR expression but its interpretation is confounded by the lack of non-standard techniques. Other approaches for measuring EGFR expression can be considered at best exploratory at this point. Further work is needed to identify how EGFR contributes to carcinogenic and metastatic processes. As tumours that appear to be EGFR negative can respond to cetuximab, there is some doubt as to the usefulness of immunohistochemistry as a screen to select patients for treatment. Histopathology will continue to be essential for unravelling the role of this enigmatic molecule and refining its status as a legitimate target in cancer therapy.
肿瘤中表皮生长因子受体（EGFR）的过表达与侵袭性疾病及不良临床预后相关。理论上，肿瘤的EGFR状态可提示对EGFR靶向治疗的反应可能性。然而，临床数据并不支持EGFR表达与对EGFR靶向治疗西妥昔单抗、吉非替尼和厄洛替尼的反应之间存在关联。最近，已证明看似缺乏EGFR表达的患者对西妥昔单抗有反应。这种矛盾现象的可能原因包括检测系统缺乏敏感性导致的假阴性结果、肿瘤内EGFR表达的异质性以及介导对酪氨酸激酶抑制剂反应的特定突变。免疫组织化学是检测EGFR表达最可靠的方法，但其解读因缺乏标准化技术而受到干扰。目前，其他测量EGFR表达的方法充其量只能算是探索性的。需要进一步开展工作来确定EGFR如何促进致癌和转移过程。由于看似EGFR阴性的肿瘤可对西妥昔单抗产生反应，因此对于免疫组织化学作为筛选患者进行治疗的有用性存在一些疑问。组织病理学对于阐明这个神秘分子的作用以及完善其作为癌症治疗中合理靶点的地位仍将至关重要。
