Epidermal growth factor receptor mutations in multicentric lung adenocarcinomas and atypical adenomatous hyperplasias
Epidermal growth factor receptor mutations in multicentric lung adenocarcinomas and atypical adenomatous hyperplasias
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DOI：
10.1097/jto.0b013e31816b4b14
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发表时间：
2008-05-01
影响因子：
20.4
通讯作者：
Kobayashi, Toshiaki
中科院分区：
文献类型：
--
作者：
Ikeda, Koei;Nomori, Hiroaki;Kobayashi, Toshiaki
背景资料：多中心肺腺癌（AD）、细支气管肺泡癌（BAC）和非典型腺瘤样增生（AAH）发生发展的机制尚不清楚。在这项研究中，我们分析了表皮生长因子受体（EGFR）突变的情况下，多中心的AD，BAC，AAH，揭示EGFR突变的作用，在其generations and progressions.Method：97 AAH，BAC，或AD病变小于3厘米的大小在26例手术切除。采用肽核酸锁核酸聚合酶链反应（PNA-LNA PCR）钳夹技术，检测了26例患者中48个组织学恶性程度最高和次高的结节的EGFR突变。EGFR突变在组织学恶性程度较高的病变中更常见，即10例AD中有9例（90%），28例BAC中有16例（57%），10例AAH中有1例（10%）。在22名患者中，每名患者的两个病变均可检测EGFR突变，只有2名患者（9%）的两个病变之间具有相同的突变模式，而15名患者（68%）具有不同的状态，其余5名患者（23%）没有突变。我们的数据表明，EGFR突变似乎有助于AAH-AD序列中恶性潜能的获得，并且在每个病变和多中心AD病例中独立发生，BAC和AAH。
Background: The mechanisms of generation and progression of multicentric lung adenocarcinoma (AD), bronchioloalveolar carcinoma (BAC), and atypical adenomatous hyperplasia (AAH) in the peripheral lung is not well known. In this study, we analyzed epidermal growth factor receptor (EGFR) mutations in the cases of multicentric AD, BAC, and AAH to reveal the role of EGFR mutation in their generations and progressions.Method: Ninety-seven AAH, BAC, or AD lesions less than 3 cm in size in 26 patients were surgically resected. Of these, EGFR mutations of the nodules with the highest and the second highest grade of histologic malignancy were examined in each patient by using the peptide nucleic acid-locked nucleic acid polymerase chain reaction (PNA-LNA PCR) clamp method.Results: EGFR mutations could be examined in 48 nodules in the 26 patients. The EGFR mutations were found more frequently in lesions with higher histologic malignancy, ie, 9 of 10 ADs (90%), 16 of 28 BACs (57%), and one of 10 AAHs (10%). In 22 patients who could be examined of EGFR mutations for the two lesions in each patient, only two patients (9%) had the same mutation patterns between the two lesions, whereas 15 patients (68%) had the different statuses and the remaining five (23%) had no mutations.Conclusion: Our data demonstrated that EGFR mutations seem to contribute to the acquisition of malignant potential in the AAH-AD sequence and occur independently in each lesion and in the cases of multicentric AD, BAC, and AAH.