Frequency of driver mutations in lung adenocarcinoma from female never-smokers varies with histologic subtypes and age at diagnosis.
Frequency of driver mutations in lung adenocarcinoma from female never-smokers varies with histologic subtypes and age at diagnosis.
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女性从不吸烟者肺腺癌的驱动突变频率随组织学亚型和诊断年龄的不同而变化
DOI：
10.1158/1078-0432.ccr-11-2511
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发表时间：
2012-04-01
期刊：
影响因子：
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通讯作者：
Chen H
中科院分区：
文献类型：
--
作者：
Zhang Y;Sun Y;Pan Y;Li C;Shen L;Li Y;Luo X;Ye T;Wang R;Hu H;Li H;Wang L;Pao W;Chen H
我们之前的研究显示，90%（47/52; 95% CI：0.79-0.96）的中国从不吸烟的肺腺癌患者仅在四个基因中存在已知的致癌驱动突变：EGFR、ALK、HER 2和KRAS。在这里，我们研究了已知的驱动突变的状态，特别是在女性从不吸烟的肺腺癌。对肿瘤进行EGFR、KRAS、ALK、HER 2和BRAF突变基因分型。年龄，阶段，肿瘤分化，组织学亚型和分子变化的数据记录从349切除肺腺癌的女性从不吸烟者。我们进一步根据这些基因的突变状态比较临床病理参数。266例（76.2%）肿瘤携带EGFR突变、16例（4.6%）HER 2突变、15例（4.3%）EML 4-ALK融合、7例（2.0%）KRAS突变和2例（0.6%）BRAF突变。在单变量分析中，携带EGFR突变的患者年龄明显较大（p<0.001），而携带HER 2突变的患者年龄明显较小（p=0.036）。侵袭性粘液腺癌（IMA）中KRAS（p=0.028）和HER 2（p=0.021）突变的患病率较高。EGFR突变频率与腺泡型肿瘤呈正相关（p=0.002）。多变量分析显示，诊断时年龄较大（p=0.013）和腺泡优势亚型（p=0.005）是EGFR突变的独立预测因素。HER 2突变的独立预测因素包括年轻（p=0.030）和IMA（p=0.017）。IMA（p=0.006）和低分化（p=0.028）与KRAS突变独立相关。不吸烟女性肺腺癌中驱动突变的频率随组织学亚型和诊断时的年龄而变化。这些数据对临床试验设计和治疗策略都有影响。
Our previous study revealed that 90% (47 of 52; 95% CI: 0.79–0.96) of Chinese never-smokers with lung adenocarcinoma harbor known oncogenic driver mutations in just four genes: EGFR, ALK, HER2, and KRAS. Here, we examined the status of known driver mutations specifically in female never-smokers with lung adenocarcinoma. Tumors were genotyped for mutations in EGFR, KRAS, ALK, HER2, and BRAF. Data on age, stage, tumor differentiation, histological subtypes, and molecular alterations were recorded from 349 resected lung adenocarcinomas from female never-smokers. We further compared the clinicopathological parameters according to mutational status of these genes. Two hundred and sixty-six (76.2%) tumors harbored EGFR mutations, 16 (4.6%) HER2 mutations, 15 (4.3%) EML4-ALK fusions, seven (2.0%) KRAS mutations, and two (0.6%) BRAF mutations. In univariate analysis, patients harboring EGFR mutations were significantly older (p<0.001), whereas patients harboring HER2 mutations were significantly younger (p=0.036). Higher prevalence of KRAS (p=0.028) and HER2 (p=0.021) mutations was found in invasive mucinous adenocarcinoma (IMA). The frequency of EGFR mutations was positively correlated with acinar predominant tumors (p=0.002). Multivariate analysis revealed that older age at diagnosis (p=0.013) and acinar predominant subtype (p=0.005) were independent predictors of EGFR mutations. Independent predictors of HER2 mutations included younger age (p=0.030) and IMA (p=0.017). IMA (p=0.006) and poor differentiation (p=0.028) were independently associated with KRAS mutations. The frequency of driver mutations in never-smoking female lung adenocarcinoma varies with histological subtypes and age at diagnosis. These data have implications for both clinical trial design and therapeutic strategies.