CAJ | 학술논문

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％ CI 8.0～20.0个月),31个月(95％ CI 24.9 ～ 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.
목적 검측폐선암환자간변성림파류격매(ALK)기인중배병탐토기여림상병리특정화예후적상관성.방법 추취2008년재북경협화의원진행근치성절제적53례폐선암환자적종류석사표본,용형광원위잡교(FISH)방법검측석사종류조직중암세포적ALK기인중배상태.용갈형탐침확증조체돌변계통검측표피생장인자수체(EGFR)기인외현자18、19、20화21돌변.결과 ALK기인중배재폐선암중적발생솔위11.3％ (6/53),남성4례,녀성2례(P =0.669);양성조평균년령시58.0세,음성조위60.8세(P=0.445).기중5례표본조직학류형시선포위주형선암,1례침습성점액선암(P=1.000).EGFR기인돌변발생솔위49.1％(26/53);6례ALK기인중배양성종류균위EGFR기인야생형,ALK기인중배여EGFR야생형밀절상관,여EGFR기인활화돌변호상배척(P=0.023).ALK기인중배양성조여ALK기인중배음성중위무류생존기분별위14개월(95％ CI 8.0～20.0개월),31개월(95％ CI 24.9 ～ 37.1개월);Log-rank검험유통계학차이(P=0.019),ALK기인중배여조기복발현저상관.ALK기인중배여성별、흡연사、종류대소、병리분기、조직분화급림파결전이지간몰유현저상관성.결론 ALK기인중배여EGFR야생형상관,여EGFR돌변호척;ALK중배환자가능여조기복발상관.
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 mucinous 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 8.0-20.0) 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.