Is the Epidermal Growth Factor Receptor Status in Lung Cancers Reflected in Clinicopathologic Features?
Is the Epidermal Growth Factor Receptor Status in Lung Cancers Reflected in Clinicopathologic Features?
复制标题
DOI：
10.1043/2008-0586-rar1.1
复制
发表时间：
2010-01-01
影响因子：
4.6
通讯作者：
Matsubara, Osamu
中科院分区：
文献类型：
--
作者：
Inamura, Kentaro;Ninomiya, Hironori;Matsubara, Osamu
背景：表皮生长因子受体(EGFR)酪氨酸激酶抑制剂是分子靶向药物，对带有EGFR突变的非小细胞肺癌创新有效。表皮生长因子受体是一种与配体结合形成二聚体的跨膜受体。然后，它们通过酪氨酸激酶活性激活受体自动磷酸化来刺激信号。自身磷酸化触发细胞内通路，促进恶性转化。临床上最先进的EGFR抑制策略包括小分子抑制细胞内酪氨酸激酶结构域(吉非替尼和厄洛替尼)和单抗介导的细胞外配体结合域阻断(西妥昔单抗)。带有EGFR突变的肺癌在女性、亚裔和非吸烟者中很常见；因此，他们可以从EGFR酪氨酸激酶抑制剂中受益。目的：调查组织病理学结果并检查与EGFR突变的相关性。我们主要关注组成细胞类型(鞋钉型、柱状型和多角型)以及细支气管肺泡癌成分和微乳头型的存在或不存在。虽然可以通过各种方法检测EGFR突变，包括聚合酶链式反应-入侵者试验或直接测序，但这些方法都不方便。数据来源-回顾已发表的文献。结论-详细的病理学检查显示，EGFR突变与细支气管肺泡癌成分、微乳头模式和鞋钉细胞类型之间存在显著的基因-表型相关性。我们的结论是，这些特征性的组织学特征可以很好地预测EGFR突变，具有这些特征的患者可能是EGFR酪氨酸激酶抑制剂治疗的良好候选者，并可能从中受益。(ARCH Pathol Lab Med.2010；134：66-72)
Context.-Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors are molecular-targeted drugs that are innovatively effective for non-small cell lung carcinomas with EGFR mutations. Epidermal growth factor receptor is a transmembrane receptor forming dimers on ligand binding. These then stimulate signals by activating receptor autophosphorylation through tyrosine kinase activity. Autophosphorylation triggers intracellular pathways facilitating malignant conversion. The most clinically advanced EGFR inhibition strategies include small-molecule inhibition of the intracellular tyrosine kinase domain (gefitinib and erlotinib) and monoclonal antibody-mediated blockade of the extracellular ligand-binding domain (cetuximab). Lung cancers with EGFR mutations are prevalent among patients who are female, of Asian ethnicity, and nonsmokers; thus, they can obtain benefit from EGFR tyrosine kinase inhibitors.Objective.-To survey histopathologic findings and examine correlations with EGFR mutations. We mainly focused on component cell types (hobnail, columnar, and polygonal) and presence or absence of bronchioloalveolar carcinoma elements and a micropapillary pattern. Although EGFR mutations can be detected by various methods, including polymerase chain reaction-Invader assay or direct sequencing, these are inconvenient.Data Sources.-Review of the published literature.Conclusion.-Detailed pathologic examination showed significant genotype-phenotype correlations between EGFR mutations and presence of a bronchioloalveolar carcinoma component, a micropapillary pattern, and the hobnail cell type. We conclude that these characteristic histologic features are good predictors of EGFR mutations, and patients with these features might be good candidates for and could benefit from therapy with EGFR tyrosine kinase inhibitors. (Arch Pathol Lab Med. 2010; 134: 66-72)