Distinctive evaluation of nonmucinous and mucinous subtypes of bronchioloalveolar carcinomas in EGFR and K-ras gene-mutation analyses for Japanese lung adenocarcinomas -: Confirmation of the correlations with histologic subtypes and gene mutations
Distinctive evaluation of nonmucinous and mucinous subtypes of bronchioloalveolar carcinomas in EGFR and K-ras gene-mutation analyses for Japanese lung adenocarcinomas -: Confirmation of the correlations with histologic subtypes and gene mutations
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DOI：
10.1309/wvxfgaflaux48du6
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发表时间：
2007-07-01
影响因子：
3.5
通讯作者：
Miyagi, Yohei
中科院分区：
文献类型：
--
作者：
Sakuma, Yuji;Matsukuma, Shoichi;Miyagi, Yohei
尽管肺腺癌与表皮生长因子受体 (EGFR) 基因突变和对 EGFR 酪氨酸激酶抑制剂的敏感性相关，但细支气管肺泡癌 (BAC) 成分和/或亚型是否影响这些关联仍不清楚。我们的目的是阐明 EGFR 基因突变和 BAC 成分之间的相关性，并建立组织学特征作为突变的可靠预测因子。我们使用环混合迁移率变动分析（一种基于高度灵敏的聚合酶链式反应的方法）检查了 141 例非小细胞肺癌 (NSCLC)，包括 118 例腺癌，检测 EGFR 基因外显子 19 和 21 的突变以及 K-ras 基因密码子 12 的突变。腺癌被细分为具有非粘液性或粘液性 BAC 成分的亚型和不具有 BAC 成分的亚型。 在 NSCLC 中，75 例（53.2%）检测到 EGFR 突变，并且与腺癌、女性和从不吸烟显着相关。在腺癌中，非粘液性和粘液性 BAC 成分分别与 EGFR 和 K-ras 基因突变显着相关。由于即使在大多数纯非粘液性 BAC（即原位肺腺癌）中也检测到 EGFR 突变，因此 EGFR 突变被认为是非粘液性 BAC 肿瘤发病机制中的关键事件。
Although adenocarcinomas of the lung are associated with epidermal growth factor receptor (EGFR) gene mutations and sensitivity to EGFR tyrosine kinase inhibitors, it remains unclear whether bronchioloalveolar carcinoma (BAC) components and/or subtypes affect these associations. We aimed to clarify correlations between EGFR gene mutations and BAC components and to establish the histologic features as reliable predictorsfor the mutations. We examined 141 non-small cell lung cancers (NSCLCs), including 118 adenocarcinomas, for mutations in exons 19 and 21 of the EGFR gene together with mutations in codon 12 of the K-ras gene using loop-hybrid mobility shift assays, a highly sensitive polymerase chain reaction-based method. Adenocarcinomas were subdivided into subtypes with a nonmucinous or mucinous BAC component and those without BAC components.In NSCLCs, EGFR mutations were detected in 75 cases (53.2%) and were significantly associated with adenocarcinoma, female sex, and never smoking. Among adenocarcinomas, nonmucinous and mucinous BAC components were significantly associated with EGFR and K-ras gene mutations, respectively. Because EGFR mutations were detected even in most pure nonmucinous BACs, ie, lung adenocarcinoma in situ, EGFR mutation is considered a critical event in the pathogenesis of nonmucinous BAC tumors.