Tumor grafts derived from patients with head and neck squamous carcinoma.

Head and neck squamous cell carcinoma (HNSCC) is a deadly and disfiguring disease for which better systemic therapy is desperately needed. The development of new therapies for HNSCC and the understanding of its biology both depend upon clinically relevant animal models. An increasingly promising xenograft model, the patient derived xenograft (PDX), is developed by surgically implanting tumor tissue directly from a patient into an immunocompromised mouse. We transplanted 30 HNSCC primary tumors directly into mice. The histology and stromal components were analyzed using immunohistochemistry. Gene expression analysis with Affymetrix U133A-microarrays was conducted on patient tumors, including third generation and one tenth generation PDX; one PDX-derived cell line; and 2 established HNSCC cell lines. Five of 30 (17%) transplanted tumors could be serially passaged and used for therapeutic and mechanistic studies. One cell line has been established from a tongue primary. The tumors maintained the histologic appearance of the parent tumor although human stromal components were lost upon engraftment. One PDX model was derived from an HPV-positive tumor. From the >54,000 probes tested, there were widespread differences in gene expression between the tumors growing in mice vs. the corresponding human tumors from which they were derived. For genes differing between parent tumors and human cell lines in culture, the PDXs expression pattern was very similar to that of the parent tumors. There were also widespread expression differences between the human tumors that subsequently grew in mice vs. those that did not - suggesting that this model enriches for cancers with distinct biological features. Our results demonstrate the feasibility of a PDX model of HNSCC. Gene expression patterns suggest that the PDX more closely recapitulated the parental tumor than do cells in culture. The histology of the tumors in mice is similar to that of the same tumor in humans. Additionally, gene expression patterns and histology are stable over multiple generations.

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Peng S, Creighton CJ, Zhang Y, Sen B, Mazumdar T, Myers JN, Lai SY, Woolfson A, Lorenzi MV, Bell D, Williams MD, Johnson FM