肺腺癌间变性淋巴瘤激酶基因重排及其与临床病理特征的关系  

Clinicopathologic correlation and ALK rearrangement in adenocarcinoma of lung

作　　者：刘平平[1] 王翠萍[1] 武莎斐[1] 高洁[1] 曾瑄[1] 

机构地区：[1]中国医学科学院北京协和医学院北京协和医院病理科,100730

出　　处：《中华病理学杂志》2014年第4期241-245,共5页Chinese Journal of Pathology

摘　　要：目的检测肺腺癌患者间变性淋巴瘤激酶（ALK）基因重排并探讨其与临床病理特征和预后的相关性。方法抽取2008年在北京协和医院进行根治性切除的53例肺腺癌患者的肿瘤石蜡标本，用荧光原位杂交（FISH）方法检测石蜡肿瘤组织中癌细胞的ALK基因重排状态。用蝎形探针扩增阻滞突变系统检测表皮生长因子受体（EGFR）基因外显子18、19、20和21突变。结果ALK基因重排在肺腺癌中的发生率为11．3％（6／53），男性4例，女性2例（P：0．669）；阳性组平均年龄是58．0岁，阴性组为60．8岁（P=0．445）。其中5例标本组织学类型是腺泡为主型腺癌，1例侵袭性黏液腺癌（P=1．000）。EGFR基因突变发生率为49．1％（26／53）；6例ALK基因重排阳性肿瘤均为EGFR基因野生型，ALK基因重排与EGFR野生型密切相关，与EGFR基因活化突变互相排斥（P=0．023）。ALK基因重排阳性组与ALK基因重排阴性中位无瘤生存期分别为14个月（95％CI8．0～20．0个月），31个月（95％C124．9—37．1个月）；Log—rank检验有统计学差异（P=0．019），ALK基因重排与早期复发显著相关。ALK基因重排与性别、吸烟史、肿瘤大小、病理分期、组织分化及淋巴结转移之间没有显著相关性。结论ALK基因重排与EGFR野生型相关，与EGFR突变互斥；ALK重排患者可能与早期复发相关。Objective To investigate ALK gene rearrangements in lung adenocarcinomas in correlation with clinicopathologic parameters including prognosis. Methods Fluorescence in situ hybridization （FISH） was used to detect ALK gene rearrangements in 53 cases of lung adenocarcinomas. Mutations in exons 18, 19, 20 and 21 of EGFR were analyzed by Scorpion amplification refractory mutation system （Scorpions ARMS）. Results In a cohort of 53 lung adenocarcinomas, ALK gene rearrangements were identified in 6 tumors （11.3%）, including 4 male and 2 female patients. Five were acinar predominant adenocarcinomas and one was mutinous adenocarcinoma （ P = 1. 000 ）. All tumors with the ALK rearrangements had the wild-type epidermal growth factor receptor （EGFR） gene （ P = 0. 023 ）. The median time of disease-free survival （DFS） in ALK positive patients and negative patients were 14 months （95% CI 8.0-20. O） and 31 months （95% CI 24. 9-37.1 ）, respectively and the difference was significant （Log-rank test, P =0. 019）. ALK gene rearrangements were significantly associated with early recurrence, but not tumor size, pathologic stages, histological differentiation and lymph node metastasis. Conclusions ALK gene rearrangements are present at a higher frequency in lung adenocarcinomas of the Chinese patients. ALK gene rearrangements are mutually exclusive with EGFR mutations and associated with early tumor recurrence.

关 键 词：肺肿瘤 腺癌 基因融合 

分 类 号：R734.2[医药卫生—肿瘤]