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男性肺腺癌患者肿瘤标本中 EGFR 外显子 19 缺失和 L858R 的发生率。

Incidence of EGFR exon 19 deletions and L858R in tumor specimens from men and cigarette smokers with lung adenocarcinomas.

机构信息

Memorial Sloan-Kettering Cancer Center and Weill Medical College of Cornell University, New York, NY 10065, USA.

出版信息

J Clin Oncol. 2011 May 20;29(15):2066-70. doi: 10.1200/JCO.2010.32.6181. Epub 2011 Apr 11.

Abstract

PURPOSE

EGFR mutations underlie the sensitivity of lung cancers to erlotinib and gefitinib and can occur in any patient with this illness. Here we examine the frequency of EGFR mutations in smokers and men.

METHODS

We determined the frequency of EGFR mutations and characterized their association with cigarette smoking status and male sex.

RESULTS

We tested 2,142 lung adenocarcinoma specimens for the presence of EGFR exon 19 deletions and L858R. EGFR mutations were found in 15% of tumors from former smokers (181 of 1,218; 95% CI, 13% to 17%), 6% from current smokers (20 of 344; 95% CI, 4% to 9%), and 52% from never smokers (302 of 580; 95% CI, 48% to 56%; P < .001 for ever v never smokers). EGFR mutations in former or current smokers represented 40% of all those detected (201 of 503; 95% CI, 36% to 44%). EGFR mutations were found in 19% (157 of 827; 95% CI, 16% to 22%) of tumors from men and 26% (346 of 1,315; 95% CI, 24% to 29%) of tumors from women (P < .001). EGFR mutations in men represented 31% (157 of 503; 95% CI, 27% to 35%) of all those detected.

CONCLUSION

A large number of EGFR mutations are found in adenocarcinoma tumor specimens from men and people who smoked cigarettes. If only women who were never smokers were tested, 57% of all EGFR mutations would be missed. Testing for EGFR mutations should be considered for all patients with adenocarcinoma of the lung at diagnosis, regardless of clinical characteristics. This strategy can extend the use of EGFR tyrosine kinase inhibitors to the greatest number individuals with the potential for substantial benefit.

摘要

目的

表皮生长因子受体(EGFR)突变是导致肺癌对厄洛替尼和吉非替尼敏感的基础,可发生于任何此类疾病患者。本研究旨在检测吸烟者和男性中 EGFR 突变的频率。

方法

我们检测了 2142 例肺腺癌标本中 EGFR 外显子 19 缺失和 L858R 突变的情况,并分析了其与吸烟状态和性别之间的关系。

结果

在 1218 例曾吸烟者肿瘤中发现 181 例(15%;95%CI:13%17%)、344 例现吸烟者肿瘤中发现 20 例(6%;95%CI:4%9%)、580 例从不吸烟者肿瘤中发现 302 例(52%;95%CI:48%56%)存在 EGFR 突变(从不吸烟者比曾吸烟者的 EGFR 突变率显著更高,P<0.001)。曾吸烟者或现吸烟者的 EGFR 突变占所有检测到的 EGFR 突变的 40%(201/503;95%CI:36%44%)。在 827 例男性肿瘤中发现 157 例(19%;95%CI:16%22%)、在 1315 例女性肿瘤中发现 346 例(26%;95%CI:24%29%)存在 EGFR 突变(男性比女性的 EGFR 突变率显著更高,P<0.001)。男性 EGFR 突变占所有检测到的 EGFR 突变的 31%(157/503;95%CI:27%~35%)。

结论

男性和吸烟者的肺腺癌标本中存在大量 EGFR 突变。如果仅对从不吸烟者的女性进行检测,那么会漏诊 57%的 EGFR 突变。在诊断时,无论患者的临床特征如何,均应考虑对所有肺腺癌患者进行 EGFR 突变检测。这种策略可以使最大数量的潜在获益患者接受 EGFR 酪氨酸激酶抑制剂的治疗。

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