存在驱动基因突变肺鳞癌患者的临床病理特征及预后分析

Driven Gene in Patients with Lung Squamous Cell Carcinoma:Analysis of Clinicopathologic Characteristics and Prognosis

背景与目的表皮生长因子受体(epidermal growth factor receptor,EGFR)、间变淋巴瘤激酶(anaplastic lymphoma kinase,ALK)以及KRAS基因是非小细胞肺癌(non-small cell lung cancer,NSCLC)常见的驱动基因。多项临床研究已证实,EGFR敏感突变及棘皮动物微管相关类蛋白4-间变淋巴瘤激酶(echinoderm microtubule-associated protein like 4-anaplastic lymphoma kinase,EML4-ALK)基因重排的晚期肺腺癌患者,一线治疗选择靶向药物优于化疗,其在总缓解率(overall response rate,ORR)、无进展生存期(progression-free survival,PFS)及生活质量方面均有明显优势。然而,在肺鳞癌患者中,目前尚无明确的基因检测位点及靶向药物来指导临床治疗。本研究旨在分析肺鳞癌患者EGFR、ALK以及KRAS基因的突变状态,以及相关的临床病理特征,从而为今后的治疗提供相应指导。方法回顾性分析已行相关驱动基因检测的肺鳞癌患者90例,利用突变扩增阻滞系统(amplification refractory mutation system,ARMS)的方法进行EGFR及KRAS基因检测,荧光原位杂交(fluorescence in situ hybridization,FISH)技术进行ALK基因融合检测。结果 90例患者均进行了EGFR及KRAS基因检测,8例患者为EGFR基因突变(8.8%);2例患者为KRAS基因突变(2.2%);18例患者通过FISH方法进行了ALK基因融合检测,1例患者存在EML4-ALK基因融合(5.6%)。女性患者的EGFR基因突变率高于男性(P=0.022)。EGFR突变及野生型患者在病理分期(P=0.042)及分化程度(P=0.003)上均有差异。以胸膜为首发转移部位的EGFR突变患者比率高于EGFR野生型患者(P=0.013)。靶向治疗与化疗对EGFR突变患者的PFS无影响(P=0.607)。结论 ALK基因融合患者应用靶向治疗后可获得理想疗效。

Background and objective It has been proven that epidermal growth factor receptor（EGFR）, anaplastic lymphoma kinase（ALK）, and KRAS are common driver genes in non-small cell lung cancer（NSCLC）. Molecular targeted therapy increases the overall response rate and progression-free survival（PFS） of patients with EGFR-sensitive mutation or echinoderm microtubule-associated protein like 4-anaplastic lymphoma kinase（EML4-ALK） fusion. However, target and targeted drugs for lung squamous cell carcinoma to indicate clinical therapy remain to be confirmed. The aim of this study was to analyze the relationship between the status of driver genes and the clinicopathologic characteristics of NSCLC. Methods A total of 90 patients were recruited and tested for EGFR, ALK and KRAS mutations. The status of EGFR and KRAS was tested by amplification refractory mutation system, and the status of ALK was tested by fluorescence in situ hybridization. Results Of the 90 patients, 8 patients had EGFR mutation（8.8%）, and 2 cases had KRAS mutation（2.2%）. EML4-ALK fusion was found in 1 of 18 patients（5.6%）. EGFR mutation occurred more frequently in females than in males（P=0.022）. Significant differences were observed in pathological stage（P=0.042） and differentiation grade（P=0.003）. No significant difference in PFS was observed between EGFR-TKI treatment and chemotherapy in EGFR mutation patients with squamous cell carcinoma of the lung（P=0.607）. Patients with EML4-ALK fusion could benefit from targeted therapy. Conclusion EML4-ALK fusion occurred more frequently than EGFR and KRAS mutations in patients with lung squamous cell carcinoma. Clinicopathologic characteristics were different between EGFR mutation and EGFR wild-type patients. The relationship between molecular targeted therapy and status of EGFR or ALK genes in patients with lung squamous cell carcinoma needs further investigation.