Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Cancer. 2012 Sep 15;118(18):4502-11. doi: 10.1002/cncr.27409. Epub 2012 Jan 26.
The discovery of distinct subsets of nonsmall cell lung cancer (NSCLC) characterized by activation of driver oncogenes has greatly affected personalized therapy. It is hypothesized that the dominant oncogene in NSCLC would be associated with distinct patterns of metastatic spread in NSCLC at the time of diagnosis.
A total of 209 consecutive patients with stage IV nonsquamous NSCLC with an EGFR (epidermal growth factor receptor) mutation (N = 39), KRAS (v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog) mutation (N = 49), ALK (anaplastic lymphoma receptor tyrosine kinase) gene rearrangement (N = 41), or wild-type for all 3 (triple negative, N = 80) were included. The percentage of patients with metastatic disease at a given site was compared between each molecular cohort (EGFR, KRAS, or ALK) and the triple negative cohort.
ALK gene rearrangement was significantly associated with pericardial disease (odds ratio [OR] = 4.61; 95% confidence interval [CI] = 1.30, 16.37; P = .02) and pleural disease (OR = 4.80; 95% CI = 2.10, 10.97; P < .001). Patients with ALK gene rearrangements (OR = 5.50; 95% CI = 1.76, 17.18; P = .003) and patients with EGFR mutations (OR = 5.17; 95% CI = 1.63, 16.43; P = .006) were predisposed to liver metastasis compared to the triple negative cohort. No molecular cohort had a predisposition to pulmonary nodules, or adrenal, bone, or brain metastasis compared to the triple negative cohort. The mean number of metastatic disease sites in patients within the ALK rearranged cohort was significantly greater than that of the triple negative cohort (mean = 3.6 sites vs 2.5 sites, P < .0001).
The results support the hypothesis that the dominant molecular oncogenes in NSCLC are associated with different biological behaviors manifesting as distinct patterns of metastatic spread at the time of diagnosis.
非小细胞肺癌（NSCLC）中驱动癌基因的激活可分为不同亚型，这一发现对个体化治疗有重要影响。目前假设 NSCLC 中的优势致癌基因与诊断时 NSCLC 转移扩散的不同模式有关。
本研究共纳入 209 例 IV 期非鳞状 NSCLC 患者，其中 EGFR（表皮生长因子受体）突变患者 39 例（N=39）、KRAS（v-Ki-ras2 Kirsten 大鼠肉瘤病毒癌基因同源物）突变患者 49 例（N=49）、ALK（间变性淋巴瘤激酶）基因重排患者 41 例（N=41）、3 种基因均未突变的患者 80 例（三阴性组，N=80）。比较各分子亚组（EGFR、KRAS 或 ALK）与三阴性组之间特定部位转移疾病的患者比例。
ALK 基因重排与心包疾病（优势比 [OR] = 4.61；95%置信区间 [CI] = 1.30，16.37；P =.02）和胸膜疾病（OR = 4.80；95% CI = 2.10，10.97；P <.001）显著相关。ALK 基因重排患者（OR = 5.50；95% CI = 1.76，17.18；P =.003）和 EGFR 突变患者（OR = 5.17；95% CI = 1.63，16.43；P =.006）与三阴性组相比，更易发生肝转移。与三阴性组相比，没有任何分子亚组有易发生肺结节、肾上腺、骨或脑转移的倾向。ALK 重排组患者的转移性疾病部位平均数明显多于三阴性组（平均数=3.6 个部位比 2.5 个部位，P<.0001）。
结果支持以下假设，即在 NSCLC 中占主导地位的分子致癌基因与不同的生物学行为相关，表现在诊断时转移扩散的不同模式。
