title: Development and characterization of HPV-positive and HPV-negative head and neck squamous cell carcinoma tumorgrafts.
abstract: OBJECTIVE
  To develop a clinically relevant model system to study head and neck squamous cell carcinoma (HNSCC), we have established and characterized a direct-from-patient tumorgraft model of human papillomavirus (HPV)-positive and HPV-negative cancers.
  
  
  METHODS
  Patients with newly diagnosed or recurrent HNSCC were consented for donation of tumor specimens. Surgically obtained tissue was implanted subcutaneously into immunodeficient mice. During subsequent passages, both formalin-fixed/paraffin-embedded as well as flash-frozen tissues were harvested. Tumors were analyzed for a variety of relevant tumor markers. Tumor growth rates and response to radiation, cisplatin, or cetuximab were assessed and early passage cell strains were developed for rapid testing of drug sensitivity.
  
  
  RESULTS
  Tumorgrafts have been established in 22 of 26 patients to date. Significant diversity in tumorgraft tumor differentiation was observed with good agreement in degree of differentiation between patient tumor and tumorgraft (Kappa 0.72). Six tumorgrafts were HPV-positive on the basis of p16 staining. A strong inverse correlation between tumorgraft p16 and p53 or Rb was identified (Spearman correlations P = 0.085 and P = 0.002, respectively). Significant growth inhibition of representative tumorgrafts was shown with cisplatin, cetuximab, or radiation treatment delivered over a two-week period. Early passage cell strains showed high consistency in response to cancer therapy between tumorgraft and cell strain.
  
  
  CONCLUSIONS
  We have established a robust human tumorgraft model system for investigating HPV-positive and HPV-negative HNSCC. These tumorgrafts show strong correlation with the original tumor specimens and provide a powerful resource for investigating mechanisms of therapeutic response as well as preclinical testing.
authors.affiliation: Department of Human Oncology, University of Wisconsin, Madison, WI 53705, USA. rkimple@humonc.wisc.edu
authors.forename: Randall J
authors.initials: RJ
authors.lastname: Kimple
authors.forename: Paul M
authors.initials: PM
authors.lastname: Harari
authors.forename: Alexandra D
authors.initials: AD
authors.lastname: Torres
authors.forename: Robert Z
authors.initials: RZ
authors.lastname: Yang
authors.forename: Benjamin J
authors.initials: BJ
authors.lastname: Soriano
authors.forename: Menggang
authors.initials: M
authors.lastname: Yu
authors.forename: Eric A
authors.initials: EA
authors.lastname: Armstrong
authors.forename: Grace C
authors.initials: GC
authors.lastname: Blitzer
authors.forename: Molly A
authors.initials: MA
authors.lastname: Smith
authors.forename: Laurel D
authors.initials: LD
authors.lastname: Lorenz
authors.forename: Denis
authors.initials: D
authors.lastname: Lee
authors.forename: David T
authors.initials: DT
authors.lastname: Yang
authors.forename: Timothy M
authors.initials: TM
authors.lastname: McCulloch
authors.forename: Gregory K
authors.initials: GK
authors.lastname: Hartig
authors.forename: Paul F
authors.initials: PF
authors.lastname: Lambert
mesh_terms: D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy / Q000821:virology*; D002471:Cell Transformation, Neoplastic / Q000187:drug effects / Q000235:genetics* / Q000473:pathology; D002945:Cisplatin / Q000008:administration & dosage; D006258:Head and Neck Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy / Q000821:virology*; D006801:Humans; D051379:Mice; D027383:Papillomaviridae / Q000187:drug effects / Q000235:genetics / Q000472:pathogenicity*; D000077195:Squamous Cell Carcinoma of Head and Neck; D014183:Transplantation, Heterologous
chemical_list: D002945:Cisplatin