非小细胞肺癌组织裸鼠皮下成瘤性与原发肿瘤临床病理特征的关系

Relationship between clinicopathological features of primary human non-small cell lung cancer and their tumorigenicity in nude mice

目的探讨非小细胞肺癌(non-small cell lung cancer,NSCLC)组织在裸鼠皮下人源性移植瘤(patient-derived xenografts,PDX)模型的成瘤性及其与原发肿瘤临床病理特征的关系。方法选取15例NSCLC组织移植于裸鼠皮下,观察成瘤情况,比较移植成瘤组和未成瘤组对应患者的临床病理特征,采用免疫组织化学法检测对应患者癌组织中p63、细胞角蛋白5/6(cytokeratin 5/6,CK5/6)、甲状腺转录因子-1(thyoid transcription factor-1,TTF-1)和Ki-67的表达。结果 15例NSCLC组织在裸鼠皮下移植后成瘤6例,成瘤率为40%。非小细胞肺癌PDX模型的成瘤性与对应患者的TNM分期和肿瘤分化程度相关(P<0.05)。成瘤组对应患者NSCLC组织中TTF-1和Ki-67蛋白阳性表达率高于未成瘤组(83%vs22%;100%vs 22%,P<0.05),p63蛋白阳性表达率则低于未成瘤组(50%vs 100%,P=0.041)。结论 NSCLC组织在裸鼠皮下的成瘤性与对应患者癌组织中p63、TTF-1、Ki-67的表达水平有关,原发肿瘤的分化程度越低、分期越晚者在祼鼠皮下更易成瘤。

Objective To investigate the relationship between the tumorigenicity of non-small cell lung cancer （NSCLC） tissue in a nude mouse model of patient-derived xenografts （PDX） and clinicopathologieal features of the primary tumor in the original patients.Methods A total of 15 NSCLC tissues were implanted subcutaneously in nude mice in order to assess their tumorigenicity,which was compared with the clinicopathologic features of the primary tumor. Expression of p63, cytokeratin 5/6 （CK5/6）, thyroid transcription factor-1 （TTF-1） and Ki-67 was detected by immunohistochemical analysis of tumor tissue from the original patients. Results Of the 15 NSCLC tissues transplanted into nude mice,6 （40%） were tumorigenic. Tumorigenicity of the PDX model was related to TNM stage and tumor differentiation in the corresponding patients（P〈0.05 ）. The rates of TTF-1 and Ki-67 expression in NSCLC tissue were significantly higher in the engrafted group than in the non-engrafted group （83% vs 22%, 100% vs 22%, P〈0.05 ）,while the rate of p63 expression was significantly lower in the engrafted group （50% vs 100% ,P=0.041 ）. Conclusions Expression intensity of p63, TFF-1, and Ki-67 in human NSCLC tissue correlates with its tumorigenicity in nude mice. Poorer differentiation of the primary tumor and more advanced stage correlate with greater tumorigenicity.