Development and Characterization of HPV-Positive and HPV-Negative Head and Neck Squamous Cell Carcinoma Tumorgrafts

• Published in: Clinical cancer research 2013-02, Vol.19 (4), p.855-864
• Main Authors: KIMPLE, Randall J, HARARI, Paul M, LEE, Denis, YANG, David T, MCCULLOCH, Timothy M, HARTIG, Gregory K, LAMBERT, Paul F, TORRES, Alexandra D, YANG, Robert Z, SORIANO, Benjamin J, MENGGANGYU, ARMSTRONG, Eric A, BLITZER, Grace C, SMITH, Molly A, LORENZ, Laurel D
• Format: Article
• Language: English
• Subjects: Animals; Antineoplastic agents; Biological and medical sciences; Carcinoma, Squamous Cell - drug therapy; Carcinoma, Squamous Cell - metabolism; Carcinoma, Squamous Cell - pathology; Carcinoma, Squamous Cell - radiotherapy; Carcinoma, Squamous Cell - virology; Cell Transformation, Neoplastic - drug effects; Cell Transformation, Neoplastic - genetics; Cell Transformation, Neoplastic - pathology; Cisplatin - administration & dosage; Head and Neck Neoplasms - drug therapy; Head and Neck Neoplasms - metabolism; Head and Neck Neoplasms - pathology; Head and Neck Neoplasms - radiotherapy; Head and Neck Neoplasms - virology; Humans; Medical sciences; Mice; Otorhinolaryngology (head neck, general aspects and miscellaneous); Otorhinolaryngology. Stomatology; Papillomaviridae - drug effects; Papillomaviridae - genetics; Papillomaviridae - pathogenicity; Pharmacology. Drug treatments; Squamous Cell Carcinoma of Head and Neck; Transplantation, Heterologous; Tumors
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.ccr-12-2746

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. 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. 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. 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.