Mucinous differentiation correlates with absence of EGFR mutation and presence of KRAS mutation in lung adenocarcinomas with bronchioloalveolar features
Mucinous differentiation correlates with absence of EGFR mutation and presence of KRAS mutation in lung adenocarcinomas with bronchioloalveolar features
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DOI：
10.2353/jmoldx.2007.060182
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发表时间：
2007-07-01
影响因子：
4.1
通讯作者：
Iafrate, A. John
中科院分区：
文献类型：
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作者：
Finberg, Karin E.;Sequist, Lecia V.;Iafrate, A. John
表皮生长因子受体基因（EGFR）的体细胞突变在肺腺癌的一个子集中检测到，特别是细支气管肺泡癌（BAC）和具有细支气管肺泡特征的腺癌（AWBF），并与酪氨酸激酶抑制剂（TKI）的临床反应相关。相反，TKI难治性肺腺癌通常具有KRAS激活突变，但缺乏EGFR突变。一些腺癌有粘液组织学，但粘液模式的临床和分子意义研究较少。我们分析了43例提交进行EGFR突变检测的BAC和AWBF肿瘤，以确定预测EGFR或KRAS突变的组织病理学特征。在30例非粘液性肿瘤中有14例（47%）检测到EGFR突变，而13例粘液性肿瘤中无EGFR突变（P = 0.003）。7例粘液腺癌中有6例（86%）检测到KRAS密码子12的错义突变，但18例非粘液腺癌中仅3例（17%）检测到KRAS密码子12的错义突变（P = 0.003）。因此，在BAC/AWBF中，粘液分化与EGFR突变的缺失和KRAS突变的存在显著相关，表明粘液BAC/AWBF不太可能对TKI有反应。因此，我们的数据表明，EGFR序列分析可以避免在BAC/AWBF时，确定真正的粘液形态，避免相关的测试成本。
Somatic mutations in the epidermal growth factor receptor gene (EGFR) are detected in a subset of lung adenocarcinomas, particularly bronchioloalveolar carcinoma (BAC) and adenocarcinoma with bronchioloalveolar features (AWBF), and correlate with clinical response to tyrosine kinase inhibitors (TKIs). in contrast, lung adenocarcinomas refractory to TKIs often have activating mutations in KRAS but lack EGFR mutations. Some adenocarcinomas have mucinous histology, but the clinical and molecular significance of the mucinous pattern is less well studied. We analyzed 43 BAC and AWBF tumors submitted for EGFR mutation testing to identify histopathological features that predicted EGFR or KRAS mutations. EGFR mutations were detected in 14 of 30 (47%) non-mucinous tumors, whereas 0 of 13 mucinous tumors harbored an EGFR mutation (P = 0.003). Missense mutations in KRAS codon 12 were detected in six of seven (86%) mucinous adenocarcinomas but only 3 of 18 (17%) nonmucinous adenocarcinomas (P = 0.003). Thus, in BAC/AWBF mucinous differentiation was significantly correlated with the absence of EGFR mutation and presence of KRAS mutation, suggesting that mucinous BACs/AWBFs are unlikely to respond to TKIs. Therefore, our data suggest that EGFR sequence analysis could be avoided in BAC/AWBF when true mucinous morphology is identified, avoiding the associated testing costs.