Discordance of Molecular Biomarkers Associated with Epidermal Growth Factor Receptor Pathway between Primary Tumors and Lymph Node Metastasis in Non-small Cell Lung Cancer
Discordance of Molecular Biomarkers Associated with Epidermal Growth Factor Receptor Pathway between Primary Tumors and Lymph Node Metastasis in Non-small Cell Lung Cancer
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DOI：
10.1097/jto.0b013e3181a94af4
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发表时间：
2009-07-01
影响因子：
20.4
通讯作者：
Ahn, Myung-Ju
中科院分区：
文献类型：
--
作者：
Park, Sarah;Holmes-Tisch, Alison J.;Ahn, Myung-Ju
简介：在非小细胞肺癌（NSCLC）患者中，为了确定最可能受益于表皮生长因子受体（EGFR）酪氨酸激酶抑制剂的患者，分子检测被认为是至关重要的。鉴于NSCLC在分子水平上的异质性，本研究旨在确定原发性肿瘤与相应淋巴结转移之间EGFR突变的差异。患者和方法：通过直接DNA测序和异双工分析，评估手术切除的101对原发性非小细胞肺癌和转移性淋巴结的EGFR突变。结果：通过直接测序或异双工分析，分别在29.7%（101例中30例）的原发肿瘤和27.7%（101例中28例）的淋巴结转移中检测到EGFR突变。通过直接测序，12例（11.9%）患者的EGFR突变在原发肿瘤和转移瘤之间不一致。在11例中，EGFR突变仅在原发肿瘤中检测到，而1例仅在淋巴结转移中检测到。异双工分析不一致17例（16.8%）。原发肿瘤阳性、淋巴结阴性10例，淋巴结阳性、原发肿瘤阴性7例。结论：相当比例的NSCLC原发肿瘤与转移淋巴结之间EGFR突变存在差异，提示肿瘤在转移过程中存在分子水平的异质性。
Introduction: For the identification of the patients who most likely benefit from epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors in non-small cell lung cancer (NSCLC), molecular assays are considered to be of paramount importance. Given the heterogeneity of NSCLC at the molecular level, this study was conducted to determine the discrepancy in EGFR mutations between primary tumors and the corresponding lymph node metastasis.Patients and Methods: Surgically resected 101 paired primary NSCLC and metastatic lymph nodes were evaluated for the EGFR mutations by direct DNA sequencing and heteroduplex analysis.Results: EGFR mutation was detected in 29.7% (30 of 101) of the primary tumors and in 27.7% of lymph node metastases (28 of 101) by either direct sequencing or heteroduplex analysis, respectively. By direct sequencing, 12 cases (11.9%) showed discordance in EGFR mutations between primary tumors and metastasis. In 11 cases, EGFR mutations were detected only in the primary tumor, whereas 1 case only in lymph node metastases. By heteroduplex analysis, 17 cases (16.8%) were discordant. Ten cases were primary tumor positive and lymph node negative, whereas seven cases were lymph node positive and primary tumor negative.Conclusions: A considerable proportion of NSCLC showed discrepancy in EGFR Mutations between primary tumors and metastatic lymph nodes, suggesting tumor heterogeneity at the molecular level during the process of metastasis.