新定义的大细胞肺癌临床病理特征及基因突变分析  

Clinicopathologic features and genetic profile of the redefined large cell lung carcinoma

作　　者：侯立坤[1] 张莉萍[1] 张伟[1] 黄焰[1] 吴伟[1] 董正伟[1] 武春燕[1] 

机构地区：[1]同济大学附属上海市肺科医院病理科,200433

出　　处：《中华病理学杂志》2017年第5期298-302,共5页Chinese Journal of Pathology

基　　金：基金项目：上海市自然科学基金（16ZR1428900）;上海市卫生与计划生育委员会基金面上项目（201440398）

摘　　要：目的 探讨新定义下的肺大细胞癌临床病理特征及基因突变情况.方法 以2015版WHO肺癌新分类的大细胞肺癌诊断标准,采用免疫组织化学[甲状腺转录因子1、Napsin A、p40、细胞角蛋白（CK）5/6、广谱CK、波形蛋白和ZEB1]和消化过碘酸雪夫（D-PAS）染色的方法,对以往诊断的303例大细胞肺癌（手术切除标本）进行回顾性分析,并对符合新定义标准的大细胞肺癌进行基因突变检测,包括表皮生长因子受体（EGFR）、KRAS、BRAF、间变性淋巴瘤激酶（ALK）、ROS1基因.结果 按新的诊断标准,经对免疫组织化学及D-PAS染色结果分析,原303例大细胞肺癌中,实性型腺癌116例（116/303,38.3%）,非角化型鳞癌49例（49/303,16.2%）,梭形细胞癌22例（22/303,7.3%）,腺鳞癌6例（6/303,2.0%）,符合新定义的大细胞癌只有110例（110/303,36.3%）.临床病理特征显示大细胞癌好发于中老年（年龄范围40~80岁）、男性（102/110,92.7%）、吸烟（64/110,58.2%）的中晚期患者.对110例符合新标准的大细胞癌进行基因检测,发现9例EGFR基因突变、10例KRAS基因突变和1例ALK基因融合,而BRAF、ROS1均为野生型.结论 按新的诊断标准,以往诊断的大细胞肺癌实则绝大多数为腺癌和非角化型鳞癌,新的诊断标准有利于临床治疗方案的确定.Objective To investigate the clinicopathologic features and genetic profile of large cell lung carcinoma （LCC） redefined by new classification.Methods Basing on 2015 WHO classification criteria in redefining large cell lung carcinoma, the expression of specific markers （TTF1, Napsin A, p40, CK5/6, CK, vimentin and ZEB1） was detected by immunohistochemistry and D-PAS staining in 303 surgically-removed lung specimens previously diagnosed as large cell lung carcinoma. The clinicopathologic and genetic characteristics （including EGFR, KRAS, BRAF, ALK and ROS1 gene mutation） were analyzed.Results Based on the new definition of LCC, 116 cases （116/303, 38.3%） of LCC formerly diagnosed were reclassified as solid adenocarcinoma, 49 cases （49/303, 16.2%） as squamous cell carcinoma, 6 cases （6/303, 2.0%） as adenosquamous carcinoma, 22 cases （22/303, 7.3%） as spindle cell carcinoma and only 110 cases （110/303, 36.3%） as large cell carcinoma. Redefined LCCs were characterized as middle-age （range 40-80）, male （102/110, 92.7%） and smoking patients （64/110, 58.2%） with intermediate-advanced stage. Among 110 cases, 9 cases with EGFR mutation and 10 cases with KRAS mutation and 1 case with ALK fusion were found. No BRAF and ROS1 alterations were identified. Conclusions According to the new classification, LCCs formerly diagnosed are mostly reclassified as adenocarcinoma and non-keratinizing squamous cell carcinoma. The newly defined LCC may significantly benefit from clinical therapy.

关 键 词：肺肿瘤 癌 大细胞 免疫组织化学 诊断 鉴别 DNA突变分析 

分 类 号：R734.2[医药卫生—肿瘤]