全自动免疫组织化学筛查间变性淋巴瘤激酶阳性非小细胞肺癌及其临床病理特征  

ALK gene fusion associated non-small cell lung cancer：automated immunostainer detection and clinicopathologic perspectives

作　　者：沈勤[1] 潘艺[2] 余波[1] 时姗姗[1] 刘标[1] 徐艳[1] 王艳芬[1] 夏秋媛[1] 饶秋[1] 陆珍凤[1] 石群立[1] 周晓军[1] 

机构地区：[1]南方医科大学南京临床医学院/南京军区南京总院病理科,210002 [2]江苏省黄山市人民医院病理科,245000

出　　处：《中华病理学杂志》2015年第3期164-169,共6页Chinese Journal of Pathology

基　　金：国家自然科学基金（81171391,81372743）

摘　　要：目的：探讨全自动免疫组织化学筛查间变性淋巴瘤激酶（ALK）基因融合非小细胞肺癌（ NSCLC）和这一分子亚型肺癌的临床病理特征。方法收集2013年1月至2014年4月期间566例非小细胞肺癌，采用Ventana抗ALK抗体及全自动免疫组织化学染色（ Ventana－IHC）方法检测ALK状态，并分析ALK基因融合NSCLC临床特征、病理形态及预后治疗。结果566例非小细胞肺癌中筛选出38例ALK阳性（6．7％）。男性患者阳性率（7．1％，25／350）大于女性组（6．0％，13／216），两者差异无统计学意义（χ2＝0．270，P＝0．604）。年龄≤60岁患者阳性率（9．9％，28／282）高于年龄＞60岁组（3．5％，10／284），两者差异有统计学意义（χ2＝9．277，P ＝0．002）。组织学形态上，腺癌（81．6％，31／38）为多，其中18例实体型为主伴黏液产生，9例腺泡型为主，1例乳头型为主，3例浸润性黏液腺癌；非腺癌包括3例鳞状细胞癌，3例腺鳞癌及1例多形性癌。不吸烟（78．9％，30／38）人数多于少量吸烟组及大量吸烟组。30例（78．9％，30／38）肿瘤最大径＞3 cm。29例（76．3％，29／38）为（Ⅲ＋Ⅳ）期。29例（76．3％，29／38）伴淋巴结转移。20例（52．6％，20／38）伴远处单／多个器官转移，最多见脑、骨转移。1例合并表皮生长因子受体基因突变。12／15接受克唑替尼治疗后病情缓解或稳定。结论 ALK基因融合肺癌是非小细胞肺癌一新的分子亚型，具有独特的临床表现和病理形态。使用Ventana抗ALK试剂及全自动免疫组织化学染色可作为检测ALK阳性非小细胞肺癌首选方法，对提高该类型肺癌的检出率及个体化治疗有着重要意义。Objective To explore the automated immunostainer screening anaplastic lymphoma kinase （ ALK） gene fusion non-small cell lung cancer （ NSCLC） and clinicopathological characteristics of the molecular subtype lung cancers.Methods Five hundred and sixty-six cases of NSCLC were collected over a 16 month period.The test for ALK was performed by Ventana automated immunostainer with anti-ALK D5F3.The histological features, treatment and outcome of patients were assessed.Results Thirty-eight cases （6.7%, 38/566） of NSCLC showed ALK gene fusion.The frequency of ALK gene fusion was higher in male （ 7.1%, 25/350 ） than that in female （ 6.0%, 13/216 ） patients, but not achieving statistical＆nbsp;significance （χ2 =0.270, P=0.604）.ALK＋NSCLC was more significantly more frequent in patients≤60 years （9.9%, 28/282） than 〉60 years （3.5%, 10/284） of age.Histologically, the ALK＋NSCLCs were mostly adenocarcinoma （81.6%, 31/38） , among which eighteen cases were solid predominant subtype with mucin production;nine cases were acinar predominant subtype;one case was papillary predominant subtype and three cases were invasive mucinous adenocarcinoma.The ALK ＋non-adenocarcinoma included three cases of squamous cell carcinoma, three cases of adenosquamous carcinoma and one case of pleomorphic carcinoma.Among the ALK＋NSCLC patients, the number of non/light cigarette smokers （86.8%, 33/38） was more than that of heavy smokers.Twenty-nine cases were stages Ⅲ and Ⅳ; twenty-nine cases showed lymph node metastasis; twenty cases showed metastases mostly to brain and bone; and one case showed EGFR gene mutation coexisting with ALK gene fusion.Twelve of fifteen patients received crizotinib therapy and remained stable.Conclusions NSCLC with ALK gene rearrangement shows distinctive clinical and histological features.Ventana-IHC may be a feasible and valid technique for detection of ALK rearrangement in NSCLC.

关 键 词：癌 非小细胞肺 腺癌 免疫组织化学 间变性淋巴瘤激酶 

分 类 号：R734.2[医药卫生—肿瘤]