实性低分化肺癌167例的病理分型及其表皮生长因子受体基因突变和间变性淋巴瘤激酶检测  

Histologic subtyping of poorly-differentiated solid lung cancer with molecular testing for epidermal growth factor receptor mutation and ALK gene rearrangement： an analyses of 167 cases

作　　者：方芳 王玉霞[3] 胡松涛[2] 杨丽[2] 邸婧[2] 刘东戈[2] 吕宁[1] Fang Fang;Wang Yuxia;Hu Songtao;Yang Li;Di ring;Liu Dongge;Lyu Ning(Department of Pathology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China)

机构地区：[1]国家癌症中心/中国医学科学院 北京协和医学院肿瘤医院病理科,100021 [2]北京医院国家老年医学中心/病理科 [3]北京医院国家老年医学中心/呼吸及危重症医学科

出　　处：《中华病理学杂志》2018年第6期432-437,共6页Chinese Journal of Pathology

摘　　要：目的探讨实性低分化肺癌通过免疫组织化学和特殊染色进一步病理分型，及其表皮生长因子受体（EGFR）基因突变和间变性淋巴瘤激酶（ALK）检测情况。方法回顾分析北京医院2014年4月至2017年4月非小细胞肺癌827例，对于其中的167例实性低分化肺癌，通过黏液特殊染色（淀粉酶处理的过碘酸雪夫染色）和免疫组织化学10种抗体[细胞角蛋白（CK）7、波形蛋白、Ki-67、CK5/6、p40、甲状腺转录因子1、Napsin A、CD56、嗜铬粒素A、突触素]进一步病理分型；采用扩增阻滞突变系统（ARMS）法对EGFR基因第18、19、20、21号外显子进行基因突变检测；用免疫组织化学Ventana ALK（D5F3）检测ALK的突变并用荧光原位杂交（FISH）验证。结果167例患者中女性79例，男性88例；年龄35～77岁，中位年龄62岁。镜下〉10%的癌组织排列呈巢片状，缺乏腺癌、鳞状细胞癌（简称鳞癌）和神经内分泌癌典型的形态学排列的病例，通过免疫组织化学和特殊染色分型为腺癌64例（38.32%）、鳞癌34例（20.35%）、大细胞神经内分泌癌21例（12.57%）、复合型大细胞神经内分泌癌5例（2.99%）、腺鳞癌2例（1.20%）、大细胞癌41例（24.55%）；Ki-67阳性指数5%～65%。5例（2.99%，5/167）腺癌成分中可见EGFR突变（19del 3例、L858R 2例），2例（1.20%，2/167）腺癌免疫组织化学Ventana ALK（D5F3）阳性，经FISH验证有基因重排。结论缺乏形态分化特征的实性低分化肺癌可以通过免疫组织化学和特殊染色进一步分型和进行分子病理学检测，从而寻找分子靶点为患者提供更为精准的治疗，改善预后。ObjectiveTo study the histological subtyping of poorly differentiated solid lung cancer by using immunohistochemistry and mucin staining along with analysis of epidermal growth factor receptor （EGFR） mutation and anaplastic lymphoma kinase （ALK） gene rearrangement.MethodsAmong 827 cases of non-small cell lung cancer at Beijing Hospital from April 2014 to April 2017, 167 cases of solid poorly differentiated lung cancer were identified and histopathologically subtyped by mucin staining （D-PAS） and immunohistochemistry using 10 antibodies （CK7, vimentin, Ki-67, CK5/6, p40, TTF1, Napsin A, CD56, chromogranin A, and synaptophysin）. Paraffin embedded tumor samples were subjected to mutation analysis of exons 18, 19, 20 and 21 of the EGFR gene by amplification refractory mutation system （ARMS） method. Immunohistochemistry （Ventana D5F3） for ALK gene rearrangement was performed followed by ALK fluorescence in situ hybridization （FISH） verification.ResultsThere were 79 females and 88 males in the study cohort. The patient′s age ranged from 35 to 77 years （mean 62 years）. Cases with solid growth pattern （at least 〉10%） and without typical histological features of adenocarcinoma, squamous cell carcinoma or neuroendocrine carcinoma were further divided based on immunohistochemistry and mucin stain into 64 cases（38.32%）of adenocarcinoma, 34 cases（20.35%） squamous cell carcinoma, 21 cases（12.57%）large cell neuroendocrine carcinoma, 5 cases（2.99%）combined large cell neuroendocrine carcinoma, 2 cases（1.20%）adenosquamous carcinoma and 41 cases（24.55%）large cell carcinoma. The Ki-67 positive rate ranged from 5% to 65%. Mutations of EGFR were detected in 5 cases （2.99%, 5/167） of adenocarcinoma（19del in 3 cases and L858R in 2 cases）. Two cases（1.20%, 2/167） with ALK-rearranged were identified by immunohistochemistry （Ventana D5F3） and confirmed by ALK FISH.ConclusionsPoorly differentiated solid lung cancer without distinct morphological features can be

关 键 词：癌 非小细胞肺 受体 表皮生长因子 DNA突变分析 基因重排 免疫组织化学 实性肺癌 

分 类 号：R734.2[医药卫生—肿瘤]