13例EML4-ALK融合基因阳性非小细胞肺癌的临床病理分析

目的 探讨棘皮动物微管相关类蛋白4（EML4）-间变性淋巴瘤激酶（ALK）融合基因阳性非小细胞肺癌（NSCLC）患者的临床病理特征。方法 回顾性分析13例EML4-ALK融合基因阳性的NSCLC患者的临床病理特征，采用HE染色观察组织病理学特征，免疫组化染色法检测组织胸苷酸合成酶（TS）的表达情况，DNA扩增后直接测序法检测组织表皮生长因子受体（EGFR）及K-Ras的突变情况，并分析该亚型肺癌患者培美曲塞的疗效。结果 13例EML4-ALK融合基因阳性NSCLC患者均为腺癌，男性5例，女性8例，中位年龄48岁，4例有吸烟史。10例NSCLC组织为腺泡样结构，其中6例伴有胞内或胞外黏液；所有患者均未检出EGFR和K-Ras基因突变，3例TS高表达，10例TS低表达；7例曾接受培美曲塞化疗方案，疾病控制率为85.7％，中位疾病进展时间为5.5个月。结论 EML4-ALK融合基因阳性NSCLC多见于不吸烟的年轻女性腺癌患者，多为伴有黏液产生的腺泡样结构，不同时合并EGFR和K-Ras突变，组织中TS低表达，大部分对培美曲塞化疗较敏感。

Clinicopathological research on 13 patients with non-smaU cell lung cancer of EMIA-ALK gene positive ex- pression

Objective To explore the clinicopathological characteristics of echinoderm microtubule-associated protein-like 4- anaplastic lymphoma kinase（EML4-ALK） fusion gene-positive non-small cell lung cancer（NSCLC）. Methods The clinical and path- ological features of 13 cases of EMLA-ALK fusion gene-positive NSCLC were investigated in this retrospective analysis. Hematoxylin and eosin staining （ HE ） was used to evaluate the histopathological features. Immunohistochemical staining for thymidylate synthase （TS） was carried out. DNA amplification followed by direct sequencing was performed to detect the mutations in epidermal growth fac- tor receptor（EGFR） and K-Ras. The efficacy of pemetrexed on this subtype of NSCLC were followed up. Results Thirteen cases of EML4-ALK fusion gene-positive NSCLC were adenocarcinoma（male 5 cases, female 8 cases; median age 48 years; 4 cases with smok- ing history）. Ten cases were of acinar-like structures and 6 cases with mucus present in intracellular and extracellular. None of the tumors examined had mutations in both the EGFR and the K-Ras genes. High expression of TS were found in 3 cases and low expres- sion levels of TS in 10 cases. Seven cases received pemetrexed chemotherapy with the disease control rate of 85.7% and median time to progression of 5.5 months. Conclusion EML4-ALK-positive NSCLC is mostly found in young female adenoearcinoma patients who are non-smokers. The pathological characteristics were acinar-predominant with intra/extracytoplasmic mucin. EMIA-ALK-positive pa- tients are sensitive to pemetrexcd chemotherapy with low TS levels. EML4-ALK-positive cases are without EGFR or K-Ras mutation un- der the general condition.