肺腺癌病理类型转化特征及耐药机制分析  

Characteristics and mechanism of pathological transformation of lung adenocarcinoma

作　　者：马蓉蓉 明宗娟[1] 李维[1] 张德信[1] 杨拴盈[1] Ma Rongrong;Ming Zongjuan;Li Wei;Zhang Dexin;Yang Shuanying(The Second Affiliated Hospital of Xi′an Jiaotong University,Xi′an 710061,China)

机构地区：[1]西安交通大学附属第二医院,西安710061

出　　处：《中华肺部疾病杂志（电子版）》2022年第6期782-786,共5页Chinese Journal of Lung Diseases(Electronic Edition)

基　　金：陕西省重点研发计划(2021SF⁃039)。

摘　　要：目的分析肺腺癌转化为鳞状细胞癌(small cell lung cancer,SCC)和小细胞肺癌(squamous cell carcinoma,SCLC)的可能机制及治疗策略。方法选择2017年1月至2022年2月我院收治的肺腺癌转化为SCLC及SCC患者7例为对象,分析临床病理特征及基因检测结果,随访并记录转归及预后。结果7例肺腺癌转化前病例1未检测到驱动基因,病例3为ROS1融合,其余为EGFR突变,病例6伴随TP53、BRCA1突变;转化后SCC 5例,SCLC 2例,转化后病例1检测到ALK融合,病例3、5和病例6保持原有突变,其余病例转化后未完善基因检测;7例肺腺癌转化前TKI中位治疗时间14个月(0~74个月)。初诊时,2例SCC SCC⁃Ag升高,1例SCLC NSE升高;转化后1例SCC SCC⁃Ag升高,1例SCLC NSE水平升高约4.7倍,2例SCLC Pro⁃GRP升高约16倍。7例中位转化时间27个月(11~92个月),SCC 27个月,SCLC 11个月。化疗为基础的综合治疗,一线治疗ORR 100%,DCR 100%,转化后一线治疗中位PFS 7个月,OS为9个月,转化后SCLC与SCC的一线治疗中位PFS分别为7个月和8个月,OS为9个月和8个月;性别、吸烟、初始接受TKI治疗大于12个月、接受三代EGFR⁃TKI治疗、EGFR突变对转化时间影响无统计学意义(P>0.05)。结论病理类型转化是肺腺癌重要的耐药机制之一,SCC⁃Ag、NSE、Pro⁃GRP水平升高及TP53突变可能与病理类型转分化有关;转化后一线化疗具有临床意义。Objective To analyze the clinical features of LUAD transformed into SCC or SCLC and explore its possible molecular mechanism and treatment.Method The clinical characteristics and genetic tests of 7 LUAD patients transformed into SCC or SCLC were retrospectively analyzed.The 7 patients were followed up by telephone,and the outcome and prognosis of the patients were recorded.Result Before the transformation of the 7 LUAD patients,case 1 detected no driver gene,case 3 was ROS1 fusion,and the others were EGFR mutations;case 6 was accompanied by TP53 and BRCA1 mutations.After transformation,5 cases were SCC and 2 cases were SCLC;case 1 detected ALK fusion,cases 3,5 and 6 remained original mutations.The rest cases didn′t receive the genetic test after transformation.The median time of taking TKIs was 14 months(0⁃74 months).At initial diagnosis,SCC⁃Ag was higher than the upper limit of normal in 2 of the patients transformed into SCC;NSE was higher than the upper limit of normal in 1 of the patients transformed into SCLC.After transformation,SCC⁃Ag was higher than the upper limit of normal in 1 of the patients transformed into SCC;NSE was about 4.7 times higher than the initial level in 1 of the patients transformed into SCLC;Pro⁃GRP in 2 SCLC patients was about 16 times higher than the initial level.The median transformation time of 7 LUAD patients was 27 months(11⁃92 months),the median transformation time of SCC was 27 months,and SCLC was 11 months.All patients received chemotherapy⁃based comprehensive therapy after transformation.The ORR of first⁃line therapy was 100%,the DCR was 100%,and the median PFS of first⁃line therapy was 7 months.the median OS after transformation was 9 months.The median OS of SCLC and SCC after transformation was 9 months and 8 months,respectively;and the median PFS of first⁃line therapy was 7 months and 8 months,respectively.Gender,smoking,initial TKI treatment for more than 12 months,third⁃generation TKI treatment,and EGFR mutation had no significant effect on transfo

关 键 词：肺腺癌 转化 小细胞肺癌 鳞状细胞癌 

分 类 号：R734.2[医药卫生—肿瘤]