High-fidelity of non-small cell lung cancer xenograft models derived from bronchoscopy-guided biopsies.

Background: At present, there are two main types of lung cancer xenograft models: those derived from stable cell lines, and patient-derived xenograft models established by surgically resected tissues. However, these animal models may not reflect the biological and genetic characteristics of advanced non-small cell lung cancer (NSCLC). We utilized bronchoscopy-guided biopsy tissues of NSCLC patients to establish xenograft models and analyzed their histopathologic and genotypic fidelity with parental tumors.

Methods: Tumor tissues of NSCLC patients taken via bronchoscope were subcutaneously implanted into mice with non-obese diabetic-severe combined immunodeficiency disease for model establishment and serial passage. The histopathology and genotype of the samples from bronchoscopy-guided biopsy-derived xenograft (BDX) models and their parental tumors were detected.

Results: Thirty BDXs out of 114 NSCLC patients (26.32%) were successfully established. Smoking status significantly affected the success rate of NSCLC BDX establishment (P = 0.010). The BDX establishment success rate in squamous cell cancer was higher than in adenocarcinoma, with no significant difference (32.00% vs. 16.21%, P = 0.112). However, the growth rate of passage 1 BDX was slower than that of passages 2 and 3. Almost all NSCLC BDXs maintained similarity to their parental tumor tissues in regard to histologic characteristics, pathological markers, and driver-gene mutations. Only one BDX model lost the epidermal growth factor receptor mutation contained in tumor parental tissue, as a result of heterogeneity.

Conclusions: NSCLC BDXs maintained high fidelity of histopathology and genotype with their original tumors. NSCLC BDXs that possess the actual status of advanced lung carcinoma should be used in preclinical research.