摘要
目的建立肺癌人源性肿瘤组织异种移植(patient-derived tumor xenograft,PDX)裸鼠模型,检测原代肺癌组织标本和第三代(F3)PDX模型组织标本内组织形态结构的变化和p63、napsin A和TTF-1的表达差异性。方法取临床肺癌新鲜手术切除标本12例,裸鼠皮下移植建立PDX模型,HE染色比较原代患者肿瘤组织与移植瘤组织结构和细胞形态变化与否;免疫组化的方法检测原代组织和F3代组织标本内p63、napsin A和TTF-1的表达水平的差异性。显微镜观察。结果成功建立传至第三代的PDX模型5例,4例肺鳞癌,1例肺腺癌。PDX模型和患者原代肿瘤具有相同的组织学特点和排列结构;p63在肺鳞癌患者及其PDX模型癌细胞中表达阳性率为84.3%和96%,两者之间差异无显著性(P>0.05),而在肺腺癌中呈阴性表达。Napsin A在肺腺癌患者及其PDX F3癌细胞中阳性表达率分别为66%和72.4%,两者之间差异无显著性(P>0.05)。TTF-1在肺腺癌患者及其PDX F3癌细胞中阳性表达率分别为91%和85%,两者之间差异也无显著性(P>0.05)。Napsin A和TTF-1在肺鳞癌中均呈阴性表达。结论本实验室所建立的肺癌PDX模型基本保留了部分原代肿瘤的组织学特性,为临床前药效的个性化筛选评估以及生物标志物的鉴定提供了有效的研发资源。
Objective To establish patient-derived tumor xenograft （ PDX） models of lung cancer in nude mice, and test the changes of histomorphological architecture and the expression levels of p63, napsin A and TTF-1 in the primary lung cancer tissues and the tissues of third-generation （F3） PDX models. Methods Tissue pieces of surgical specimens from 12 lung cancer patients（8 squamous cell carcinomas and 4 adenocarcinomas）were taken and subcutaneously engrafted into nude mice to establish PDX models. Samples of the primary lung cancer tissues from patients and its PDX model in mice after the F3 generation were examined by pathology using HE staining. The changes of expression levels of p63, nap- sin A and TTF-1 were detected by immunohistochemistry. Results A total of 5 cases of the F3 PDX models were estab-lished successfully, including 4 cases of squamous cell carcinoma （SCC） and one case of adenocarcinoma （ADC）. The tissue samples of the PDX model showed the same histological features of the primary tumor tissues. The p63 protein was positively expressed in 84. 3% of the SCC tissues and 96% of the PDX models, showing a non-significant difference （ P ＆gt;0. 05）, while negatively expressed in the ADC tissues. The positive rate of napsin A protein expression was 66% of the ADC tissues and 72. 4% of the F3 PDX models, without a significant difference between them （P 〉0. 05）. The express-ing rate of TTF-1 protein was 91% of the ADC tissues and 85% of the F3 PDX models, without a significant difference （ P〉0. 05） as well. In addition, both napsin A and TTF-1 were negatively expressed in the SCC tissues. Conclusions The PDX models of lung cancers we have established retained some of the key features of the primary cancers, such as histologi-cal architecture, genomic signature, cellular heterogeneity and drug responsiveness, providing an effective resource for the research and development of personalized screening and evaluating of the drug efficacy in clinical trials and the identifica-ti
出处
《中国比较医学杂志》
北大核心
2017年第9期60-64,共5页
Chinese Journal of Comparative Medicine
