Evaluation of EGFR abnormalities in patients with pulmonary adenocarcinoma: the need to test neoplasms with more than one method
Evaluation of EGFR abnormalities in patients with pulmonary adenocarcinoma: the need to test neoplasms with more than one method
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DOI：
10.1038/modpathol.2008.182
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发表时间：
2009-01-01
期刊：
影响因子：
7.5
通讯作者：
Marchevsky, Alberto M.
中科院分区：
文献类型：
--
作者：
Gupta, Ruta;Dastane, Aditi M.;Marchevsky, Alberto M.
表现出表皮生长因子受体过表达或突变的晚期肺腺癌患者往往对酪氨酸激酶抑制剂如吉非替尼和厄洛替尼的靶向治疗反应更好。关于这些肿瘤应如何常规检测表皮生长因子受体（EGFR），以及免疫组化（IHC）、突变分析和荧光原位杂交的结果是否相互关联或是否为独立的预测变量，目前尚无共识。我们使用IHC、PCR和荧光原位杂交（FISH）检测了100例III期或IV期肺腺癌患者的EGFR异常，并使用kappa和其他统计方法对结果进行了比较。计算每种检测方法检测EGFR异常的灵敏度及其阴性预测值，以估计其他两种方法检测结果异常的存在。免疫组化、荧光原位杂交和PCR检测EGFR异常率分别为62%、40%和24%。kappa统计结果显示EGFR检测结果之间的一致性较差（IHC和PCR以及PCR和FISH的kappa值分别为0.3和0.2）。在90%以上的肿瘤细胞中发现强膜免疫反应性与扩增或多体性相关。当PCR作为单一检测时，可能会低估EGFR异常的存在，而EGFR异常可能显著预测对酪氨酸激酶抑制剂的反应。需要标准化的方法，EGFR检测晚期肺腺癌患者进行了讨论。
Patients with advanced pulmonary adenocarcinoma exhibiting overexpression or mutation of epidermal growth factor receptor tend to respond better to targeted therapy with tyrosine kinase inhibitors such as gefitinib and erlotinib. There is no consensus regarding how these neoplasms should be routinely tested for epidermal growth factor receptor ( EGFR) and whether the results of immunohistochemistry (IHC), mutation analysis and fluorescent in situ hybridization correlate with each other or are independent predictive variables. We tested 100 pulmonary adenocarcinomas from patients with stage III or IV disease for EGFR abnormalities using IHC, PCR and fluorescent in situ hybridization (FISH) and compared the results using kappa and other statistical methods. The sensitivity of each test to detect an EGFR abnormality and its negative predictive value to estimate the presence of an abnormal test result by the other two methods were calculated. Abnormal EGFR test results were found in 62, 40 and 24% by IHC, FISH and PCR, respectively. kappa statistics yielded poor concordance between the results of the EGFR tests (kappa = 0.3, and 0.2 for IHC and PCR and for PCR and FISH, respectively). Strong membranous immunoreactivity in more than 90% of the tumor cells was found to correlate with amplification or polysomy. PCR when used as a single test is likely to underestimate the presence of EGFR abnormalities that may significantly predict response to tyrosine kinase inhibitors. The need to standardize the approach to EGFR testing in patients with advanced pulmonary adenocarcinoma is discussed.