Guangdong Lung Cancer Institute, Guangdong General Hospital and Guangdong Academy of Medical Sciences, Guangzhou, China.
Clin Lung Cancer. 2010 May;11(3):160-8. doi: 10.3816/CLC.2010.n.020.
Epidermal growth factor receptor (EGFR) mutations may accumulate during the multistage progression of bronchioloalveolar carcinoma (BAC), leading to heterogeneity within the tumor. This study sought to determine whether metachronous adenocarcinomas with a BAC component emerging in the lung field arise from a single or multiple clones in the same individual.
Samples of adenocarcinomas exhibiting various degrees of BAC were obtained by thoracotomy. Sequential specimens were obtained upon detection of metachronous lesions in the lung field. Genomic DNA was extracted from specimens, and the presence of activating mutations in EGFR was determined via direct sequencing. Our pathologic findings, sequential image information, and genetic data were compared to track evidence of cancer evolution.
Based on EGFR gene analyses of tumor specimens from 431 patients, 17 cases of sequential BAC-related adenocarcinomas, obtained by thoracotomy, were noteworthy. Upon alteration of the BAC/adenocarcinoma components, the EGFR tyrosine kinase inhibitor-untreated series, which had at least one episode of an EGFR-activating mutation, represented 3 potential hypotheses: no significant EGFR evolution for a single clone, genetic alterations from mutant to wild-type EGFR for multifocal lesions, or a switch from wild-type to mutant EGFR, leading to indeterminable cancer progression.
Genetic analysis, in conjunction with pathologic and radiologic diagnoses, can be used to explore the origin of multifocal BAC. The single-clone model indicates subsequent disease progression, whereas genetic alterations from mutations to wild-type EGFR are suggestive of second primary carcinoma. In cases when additional lesions emerge after the radical resection of BAC-related lung cancer, sequential tumor samples should be obtained for further evaluation.
表皮生长因子受体 (EGFR) 突变可能在细支气管肺泡癌 (BAC) 的多阶段进展中累积，导致肿瘤内的异质性。本研究旨在确定在肺野中出现 BAC 成分的同时性腺癌是否来自同一个体的单个或多个克隆。
通过开胸术获得表现出不同程度 BAC 的腺癌样本。在检测到肺野中的同时性病变时，获得连续标本。从标本中提取基因组 DNA，并通过直接测序确定 EGFR 激活突变的存在。我们将病理发现、连续的图像信息和遗传数据进行比较，以追踪癌症进化的证据。
基于对 431 例患者肿瘤标本的 EGFR 基因分析，我们注意到 17 例经开胸术获得的连续 BAC 相关腺癌。在 BAC/腺癌成分改变后，未接受 EGFR 酪氨酸激酶抑制剂治疗的系列，至少有一次 EGFR 激活突变，代表了 3 个潜在假设：单一克隆没有明显的 EGFR 进化、多灶性病变中从突变型到野生型 EGFR 的遗传改变，或从野生型到突变型 EGFR 的转变，导致癌症进展无法确定。
遗传分析结合病理和放射学诊断可用于探索多灶性 BAC 的起源。单克隆模型表明随后的疾病进展，而从突变到野生型 EGFR 的遗传改变提示第二原发性癌。在 BAC 相关肺癌根治性切除后出现额外病变的情况下，应获取连续的肿瘤样本进行进一步评估。
