Abstract
Patient-derived xenograft (PDX) models generated from surgical specimens are gaining popularity as preclinical models of cancer. However, establishment of PDX lines from small cell lung cancer (SCLC) patients is difficult due to very limited amount of available biopsy material. We asked whether SCLC cells obtained from endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) could generate PDX lines that maintained the phenotypic and genetic characteristics of the primary tumor. Following successful EBUS-TBNA sampling for diagnostic purposes, we obtained an extra sample for cytologic analysis and implantation into the flanks of immunodeficient mice. Animals were monitored for engraftment for up to 6 months. Histopathologic and immunohistochemical analysis, and targeted next-generation re-sequencing, were then performed in both the primary sample and the derivative PDX line. A total of 12 patients were enrolled in the study. EBUS-TBNA aspirates yielded large numbers of viable tumor cells sufficient to inject between 18,750 and 1,487,000 cells per flank, and to yield microgram quantities of high-quality DNA. Of these, samples from 10 patients generated xenografts (engraftment rate 83%) with a mean latency of 104 days (range 63–188). All but one maintained a typical SCLC phenotype that closely matched the original sample. Identical mutations that are characteristic of SCLC were identified in both the primary sample and xenograft line. EBUS-TBNA has the potential to be a powerful tool in the development of new targeting strategies for SCLC patients by providing large numbers of viable tumor cells suitable for both xenografting and complex genomic analysis.
Highlights
Small cell lung cancer (SCLC) accounts for approximately 15% of all thoracic malignancies [1]
Immunohistochemical staining of cell block sections was performed for Synaptophysin, CD56 and Thyroid Transcription Factor 1 (TTF1) in 8, 2 and 1 cases respectively
Patient-derived xenograft (PDX) models have recently emerged as a way of more accurately modelling therapeutic responses [5,6,7] outcome [12,19] and as source of high quality material for next-generation sequencing [20]
Summary
Small cell lung cancer (SCLC) accounts for approximately 15% of all thoracic malignancies [1]. Patients with disease confined to the chest are treated with chemo-radiotherapy, whereas patients with advanced disease are treated with chemotherapy alone [2]. Platinum-based doublet chemotherapy induces complete responses in up to 20%, whereas combined chemoradiotherapy in disease limited to the chest produces complete responses in up to 50% of patients [3]. Since surgical resection of SCLC is uncommon, diagnosis and biomarker studies rely heavily on samples obtained by percutaneous fine needle aspiration or bronchoscopic forceps biopsy [1]. Both techniques provide precious little material for researchers, leading
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