肺腺癌7371例间变性淋巴瘤激酶融合蛋白表达及其临床病理特征分析

Expression of ALK protein in 7 371 pulmonary adenocarcinoma samples, with analysis of clinicopathologic features

目的探讨Ventana免疫组织化学法检测肺腺癌间变性淋巴瘤激酶（ ALK）融合蛋白的表达情况及其与患者临床病理学特征的关系。方法收集上海交通大学附属胸科医院2013年7月至2015年9月期间肺腺癌病例7371例，利用Ventana抗ALK（D5F3）试剂盒在BenchMark全自动免疫组织化学平台上行ALK融合蛋白检测，并分析其临床病理学特征。结果7371例肺腺癌标本中ALK融合蛋白阳性446例（6.05％）。活检小标本阳性率高于手术标本[9.02％（153／1696）比5.16％（293／5675），P＜0.01]。患者年龄、标本类型、吸烟史与ALK融合蛋白检测结果显著相关。各年龄组的ALK融合蛋白阳性率随患者年龄减小而依次增高，其中＜30岁年龄组ALK融合蛋白阳性率达45.45％（10／22）。原位腺癌 ALK 融合蛋白阳性率为0（0／92）、微浸润性腺癌0.48％（2／418）、浸润性腺癌5.63％（291／5165）。各组织亚型间ALK融合蛋白阳性率差异有统计学意义（P＜0.01），浸润性黏液腺癌最高，为18.29％（45／246），实性为主浸润性腺癌次之，为14.26％（88／617）。结论 ALK融合蛋白阳性更常见于年轻的肺腺癌患者，特别是小于30岁的患者；在早期肺腺癌中罕见ALK融合蛋白阳性；浸润性黏液腺癌和实性为主型浸润性腺癌ALK融合蛋白阳性率明显高于其他亚型为主的浸润性腺癌。

Objective To study the expression of ALK protein in pulmonary adenocarcinoma as detected by Ventana immunohistochemistry, with correlation of clinicopathologic features. Methods Immunohistochemical study for ALK protein using Ventana ALK （ D5F3） kit was carried in 7 371 pulmonary adenocarcinoma samples.The clinicopathologic features were subsequently analyzed.Results ALK fusion protein was detected in 446 of the 7 371 lung adenocarcinoma samples studied （ 6.05%） .The ALK positivity rate in small biopsy samples was higher than that in surgical specimens [ 9.02% （ 153/1 696 ） versus 5.16%（293/5 675）;P〈0.01] .ALK fusion protein expression correlated with patient age, sample type and smoking history.ALK positivity rate in each age group increased with younger patient age.ALK positivity rate was 45.45%（10/22） in patients younger than 30 years old.The positivity rate of ALK fusion protein in adenocarcinoma in-situ, minimally invasive adenocarcinoma and invasive adenocarcinoma was 0, 0.48%（2/418） and 5.63% （291/5 165）, respectively.The differences of ALK positivity rate amongst different subtypes had statistical significance （ P〈0.01 ）.Invasive mucinous adenocarcinoma had highest ALK positivity rate, followed by invasive adenocarcinoma with predominantly solid pattern.Conclusions ALK fusion protein is more often found in young patients with pulmonary adenocarcinoma, especially in those younger than 30 years old.ALK fusion protein is rarely expressed in early-stage pulmonary adenocarcinoma. Invasive mucinous adenocarcinoma and invasive adenocarcinoma with solid pattern have higher ALK positivity rate than other adenocarcinoma subtypes.