Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenvironment, Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital, Heping District, Tianjin, China.
PLoS One. 2013;8(1):e52093. doi: 10.1371/journal.pone.0052093. Epub 2013 Jan 14.
The EML4-ALK fusion gene has been recently identified in a small subset of non-small cell lung cancer (NSCLC) patients who respond positively to ALK inhibitors. The characteristics of the EML4-ALK fusion gene in Chinese patients with NSCLC are poorly understood. Here, we report on the prevalence of EML4-ALK, EGFR status and KRAS mutations in 208 Chinese patients with NSCLC. EGFR mutations were found in 24.5% (51/208) of patients. In concordance with previous reports, these mutations were identified at high frequencies in females (47.5% vs 15.0% in males; P<0.05); never-smokers (42.3% vs 13.9% in smokers; P<0.05), and adenocarcinoma patients (44.2% vs 8.0% in non-adenocarcinoma patients; P<0.05). There were only 2.88% (6/208) patients with KRAS mutations in our study group. We identified 7 patients who harbored the EML4-ALK fusion gene (3.37%, 7/208), including 4 cases with variant 3 (57.1%), 2 with variant 1, and 1 with variant 2. All positive cases corresponded to female patients (11.5%, 7/61). Six of the positive cases were non-smokers (7.69%, 6/78). The incidence of EML4-ALK translocation in female, non-smoking adenocarcinoma patients was as high as 15.2% (5/33). No EGFR/KRAS mutations were detected among the EML4-ALK positive patients. Pathological analysis showed no difference between solid signet-ring cell pattern (4/7) and mucinous cribriform pattern (3/7) in ALK-positive patients. Immunostaining showed intratumor heterogeneity of ALK rearrangement in primary carcinomas and 50% (3/6) of metastatic tumors with ALK-negative staining. Meta-analysis demonstrated that EML4-ALK translocation occurred in 4.84% (125/2580) of unselected patients with NSCLC, and was also predominant in non-smoking patients with adenocarcinoma. Taken together, EML4-ALK translocations were infrequent in the entire NSCLC patient population, but were frequent in the NSCLC subgroup of female, non-smoker, adenocarcinoma patients. There was intratumor heterogeneity of ALK rearrangement in primary carcinomas and at metastatic sites.
EML4-ALK 融合基因在一小部分非小细胞肺癌（NSCLC）患者中被发现，这些患者对 ALK 抑制剂有积极的反应。在中国 NSCLC 患者中，EML4-ALK 融合基因的特征尚未得到很好的了解。在这里，我们报告了 208 例中国 NSCLC 患者中 EML4-ALK、EGFR 状态和 KRAS 突变的流行情况。在 208 例患者中，发现 EGFR 突变占 24.5%（51/208）。与之前的报告一致，这些突变在女性中高频出现（47.5%比男性的 15.0%；P<0.05）；从不吸烟者（42.3%比吸烟者的 13.9%；P<0.05）和腺癌患者（44.2%比非腺癌患者的 8.0%；P<0.05）。在我们的研究组中，只有 2.88%（6/208）的患者有 KRAS 突变。我们发现 7 例患者存在 EML4-ALK 融合基因（3.37%，7/208），其中 4 例为变异 3（57.1%），2 例为变异 1，1 例为变异 2。所有阳性病例均为女性（11.5%，7/61）。阳性病例中 6 例为不吸烟者（7.69%，6/78）。女性、不吸烟的腺癌患者中 EML4-ALK 易位的发生率高达 15.2%（5/33）。在 EML4-ALK 阳性患者中未发现 EGFR/KRAS 突变。组织学分析显示，ALK 阳性患者的实体印戒细胞模式（4/7）和黏液性筛状模式（3/7）之间无差异。免疫染色显示，原发性癌中有 ALK 重排的肿瘤内异质性，50%（3/6）ALK 阴性转移瘤中有 ALK 阴性染色。荟萃分析表明，EML4-ALK 易位发生在未经选择的 NSCLC 患者的 4.84%（125/2580）中，在非吸烟的腺癌患者中也更为常见。总之，EML4-ALK 易位在整个 NSCLC 患者人群中并不常见，但在女性、不吸烟、腺癌患者的 NSCLC 亚组中较为常见。原发性癌和转移部位的 ALK 重排存在肿瘤内异质性。
