Dei Tos A P
Department of Pathology, Regional Hospital of Treviso, Treviso, Italy.
Int J Biol Markers. 2007 Jan-Mar;22(1 Suppl 4):S3-9.
Receptor tyrosine kinases play a major role in human carcinogenesis. Overexpression of the epidermal growth factor receptor (EGFR) has been associated with poor clinical outcome in several types of cancer. In principle, as with HER2, the EGFR status of a tumor should predict the likelihood of response to EGFR-targeted therapy. However, clinical data have failed to demonstrate a relationship between EGFR expression and response to the EGFR-targeted compounds cetuximab, gefitinib and erlotinib. Recently, patients reported to be EGFR negative have been shown to respond to cetuximab. Possible explanations include methodological failures or most likely heterogeneity and complexity of the mechanisms of EGFR-mediated molecular carcinogenesis. Immunohistochemistry is the most widely used method for measuring EGFR expression; however, its value is limited by lack of methodological standardization. Other approaches to measuring EGFR such as amplification assays are currently being introduced but need further testing before they can enter clinical practice. Mutational analysis seems also fruitful in predicting response to anti-EGFR small molecules. Further work is needed to identify how EGFR contributes to the carcinogenic and metastatic processes.
受体酪氨酸激酶在人类致癌过程中起主要作用。表皮生长因子受体（EGFR）的过表达与多种癌症的不良临床预后相关。原则上，与HER2一样，肿瘤的EGFR状态应能预测对EGFR靶向治疗的反应可能性。然而，临床数据未能证明EGFR表达与对EGFR靶向化合物西妥昔单抗、吉非替尼和厄洛替尼的反应之间存在关联。最近，据报道EGFR阴性的患者对西妥昔单抗有反应。可能的解释包括方法学上的不足，或者最有可能的是EGFR介导的分子致癌机制的异质性和复杂性。免疫组织化学是测量EGFR表达最广泛使用的方法；然而，其价值因缺乏方法学标准化而受到限制。目前正在引入其他测量EGFR的方法，如扩增检测，但在进入临床实践之前还需要进一步测试。突变分析在预测对抗EGFR小分子的反应方面似乎也很有成效。需要进一步开展工作来确定EGFR如何促进致癌和转移过程。
