间变性淋巴瘤激酶融合基因阳性肺腺癌的临床病理特征

Clinicopathological Features of Lung Adenocarcinoma Harboring Anaplastic Lymphoma Kinase Rearrangements

目的探讨间变性淋巴瘤激酶（ALK）融合基因阳性肺腺癌的临床病理特征，并分析其治疗方法和预后。方法回顾性分析2005-2014年首都医科大学附属北京胸科医院收治的34例ALK融合基因阳性肺腺癌手术患者的临床资料，采用Ventana全自动免疫组织化学染色系统对术后标本进行染色，检测ALK蛋白表达情况，同时应用DNA直接测序法检测肿瘤组织表皮生长因子受体（EGFR）的突变状态。结果34例ALK融合基因阳性肺腺癌患者中，男20例，女14例；中位年龄49岁。吸烟11例，不吸烟23例。临床分期为IA期5例，IB期1例，ⅡA期2例，ⅢA期16例，ⅢB期5例，Ⅳ期分4例，未明确分期1例。免疫组织化学染色显示，所有患者的肿瘤组织均表现为肿瘤细胞的细胞质内ALK蛋白强颗粒状着色。组织学表现为实体型为主伴黏蛋白分泌14例，腺泡样为主10例，乳头状为主6例，微小乳头状为主3例，胶质样腺癌1例，其中肿瘤组织伴有黏液分泌18例，伴有筛状结构10例，伴有印戒细胞6例。34例患者中，仅有1例为ALK融合基因阳性与EGFR基因突变（21 LSSSR）共存。有24例患者获得随访，中位无进展生存时间为11．0个月。结论ALK融合基因阳性的肺腺癌具有比较独特的临床病理特征，实体型为主伴黏蛋白分泌、腺泡样为主、印戒细胞和筛状结构是其较为典型的组织学形态，大多与EGFR基因突变不共存。

Objective To analyze the clinicopathological characteristics of patients with anaplastic lymphoma kinase （ALK） rearrangements in lung adenocarcinoma, and the clinical therapy and prognosis of the patients. Methods Clinieopathological data of 34 cases of ALK-positive patients treated in the Beijing Chest Hospital from 2005 to 2014 were reviewed. The expression of ALK proteins in the resected tumors was detected by immunohistoehemistry, and EGFR mutations were examined by polymerase chain reaction and a direct DNA sequencing method. Results Among the 34 patients, 20 were male and 14 were female, the median age was 49, and 11 were smokers and 23 were never smokers. The clinical stages of the patients were stage I A in 5 patients, I B in one patient, II A in two patients, m A in 16 patients, m B in 5 patients, 1V in 4 patients, and one patient of unknown stage. ALK-positive tumors showed strong granular staining in cell cytoplasm by immunohistochemistry. Forteen patients were solid predominant subtype with muein production, 10 of acinar predominant subtype, 6 of papillary predominant subtype, 3 of micropapillary predominant subtype, and one was of colloid variant. There were 18 cases with mucin production, 6 cases had signet-ring cell morphology, and 10 cases showed cribriform pattern. Only one patient had coexistence of ALK rearrangement and EGFR mutation （L858R at exon 21）. Of the 34 patients, 24 patients were followed up. The median follow up of the 24 patients was 11.0 months （1.7-48.7 months）. Conclusions ALK-positive tumors as a molecular subtype of lung adenoearcinoma have distinct clinicopathological features. The histological findings of ALK-positive tumors are characterized by solid predominant subtype with mucin production, acinar predominant subtype, signet-ring cells and cribriform structures. They were rarely comutated with EGFR mutation.