Setup of a head and neck cancer biobank and patient-derived xenografts - Differential engraftment of surgical specimens and endoscopic biopsies

Head & neck cancer exhibits considerable heterogeneity in biologic behaviour and therapeutic response. Patient-derived xenografts (PDX) can capture this heterogeneity maintaining morphology and molecular profiling of the original tumours, thus providing a platform for the examination of disease biology and novel therapeutic agents.

However, restricted availability of tumour samples hindered widespread utilization of PDX. Most PDX-projects include exclusively surgical specimens, because reliable engraftment from biopsies has not been reported. Sample collection is limited and excludes recurrent and metastatic cancer (that cannot be treated surgically) from preclinical models as well as future personalized medicine if surgical samples are included only. Therefore, this study investigates PDX formation from biopsies and factors contributing to engraftment.

Specimens from endoscopic biopsies and surgery were analysed for the viable tumour tissue and fragments of 3x3x3 mm³ were implanted into NSG mice (sc). This study shows that engraftment occurs in both biopsies and surgical specimens. However, the engraftment rate was lower for biopsies (22 % vs. 66 %) and engraftment took longer (12 vs. 6 weeks). After successful engraftment, growth kinetics were similar. To examine these limits in initial engraftment of biopsies, the study analyses HE histology, proliferation (Ki-67/PHH3), apoptosis (Caspase-3), immune status (PD-L1, CD8/56/68/208) and mutational profile (in-house Cancer Hotspot Panel) of the samples and the corresponding PDX. The Results may improve PDX preparation to include aggressive carcinomas, which cannot be treated by surgery. Thus, the relation of PDX-engraftment and clinical outcome might lead to the identification of novel clinical biomarkers.

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Publication History

Article published online:
10 June 2020