Department of Pulmonary Diseases, Lyon Sud Hospital Center, Claude Bernard University, Lyon, France.
Cancer. 2010 Jun 1;116(11):2682-7. doi: 10.1002/cncr.25014.
The objective of this study was to determine whether the mutation status of the v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) and epidermal growth factor receptor (EGFR) differed between primary tumors and matched distant metastases in nonsmall cell lung cancer (NSCLC).
Patients who underwent resection for both primary NSCLC and matched distant metastases were included in the study. KRAS and EGFR mutation status were assessed by polymerase chain reaction (PCR) amplification and direct sequencing on both primary tumors and metastases. For KRAS analysis, mutant-enriched PCR (ME-PCR) was performed in case of discordance between a primary tumor and its matched metastasis.
Twenty-one patients were included. No EGFR mutations were detected. KRAS mutations were detected in 6 patients (28%). In all patients, the mutations identified by direct sequencing were discordant between the primary tumor and the matched metastasis. The use of ME-PCR allowed a resolution of the discordance in 3 of the 6 cases by demonstrating the presence of low levels of mutant KRAS in lesions that were negative by direct sequencing.
Highly sensitive tools are required to identify biomarkers. The KRAS mutation status mostly was concordant between primary tumors and matched distant metastases. In a few patients, KRAS mutation status differed between different tumor sites.
本研究旨在确定非小细胞肺癌（NSCLC）中，原发肿瘤和配对的远处转移灶之间 KRAS（v-Ki-ras2 Kirsten 大鼠肉瘤病毒癌基因同源物）和表皮生长因子受体（EGFR）的突变状态是否存在差异。
本研究纳入了接受原发性 NSCLC 及配对远处转移灶切除术的患者。通过聚合酶链反应（PCR）扩增和直接测序，对原发肿瘤和转移灶进行 KRAS 和 EGFR 突变状态评估。在原发肿瘤与其配对转移灶之间存在不一致时，对 KRAS 进行分析采用突变富集 PCR（ME-PCR）。
共纳入 21 例患者。未检测到 EGFR 突变。6 例患者（28%）检测到 KRAS 突变。在所有患者中，通过直接测序鉴定的突变在原发肿瘤和配对转移灶之间存在不一致。在 6 例患者中的 3 例中，采用 ME-PCR 可解决不一致的问题，因为 ME-PCR 显示在直接测序为阴性的病变中存在低水平的突变型 KRAS。
需要使用高灵敏度的工具来识别生物标志物。KRAS 突变状态在原发肿瘤和配对的远处转移灶之间大多是一致的。在少数患者中，KRAS 突变状态在不同的肿瘤部位存在差异。
