期刊
LARYNGOSCOPE
卷 127, 期 12, 页码 2777-2783出版社
WILEY
DOI: 10.1002/lary.26679
关键词
Patient-derived xenograft; HPV; head and neck cancer; preclinical model
资金
- NIH [K08-DE022842, R21-DE024396, P01-CA098101, F32-DE024685, P30-DK050306]
- American College of Surgeons/Triological Society Clinical Scientist Development Award
Objectives/HypothesisDelineate factors impacting the creation and use of patient-derived xenografts (PDXs) of human papilloma virus-related (HPV+) head and neck squamous cell carcinomas (HNSCCs). Study DesignLaboratory-based translational study. MethodsFifty-one surgically resected HNSCCs, including 31 HPV+cancers, were implanted into NOD/SCID/IL-2R(-/-) (NSG) mice using standardized methodology. Clinical and pathologic factors were tested for association with engraftment. The gross, histologic, and molecular features of established HPV+PDXs were analyzed in comparison to their tumors of origin. ResultsNegative HPV status and perineural invasion (PNI) were independent, additive factors associated with increased PDX formation. Epstein-Barr virus-positive (EBV+) human large B-cell lymphomas grew from 32% of HPV+HNSCC cases that failed to engraft. Successfully established HPV+PDXs retained basaloid histology and often developed cystic growth patterns typical of HPV+nodal metastases. They also maintained elevated p16(INK4A) levels and expression of E6/E7 viral oncogene transcripts. ConclusionReduced engraftment by HPV+tumors lacking PNI likely results in selection biases in HNSCC PDX models. Formation of EBV+lymphomas in NSG mice further reduces the generation of HPV+models and must be ruled out before long-term use of PDXs. Nevertheless, the retention of distinctive pathologic traits and viral oncogene expression by HPV+PDXs provides a viable in vivo platform for basic and translational studies as well as a resource for generating advanced in vitro models. Level of EvidenceNA. Laryngoscope, 127:2777-2783, 2017
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