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Soon-Hyun Ahn, MD, PhD; Ying Henderson, MD, PhD; Ya’an Kang, MD, PhD; Chandrani Chattopadhyay, PhD; Paula Holton, MS; Mary Wang, MS; Katrina Briggs, BS; Gary L. Clayman, DDS, MD

Arch Otolaryngol Head Neck Surg. 2008;134(2):190-197.

Objective  To develop a reproducible orthotopic model of papillary thyroid carcinoma for the BRAF^V600E mutation (GenBank NM004333) and an RET/PTC rearrangement (GenBank M31213) that recapitulates the clinical picture in humans.

Design  In vitro and in vivo study.

Setting  Department of Head and Neck Surgery, M. D. Anderson Cancer Center.

Subjects  Eight- to 12-week-old athymic female nude mice.

Interventions  Either BRAF-mutated or RET/PTC1–rearranged papillary thyroid carcinoma cells were injected into the thyroid glands of athymic female nude mice. The mice were euthanized when the tumor burden exceeded 1.0 cm or when they exhibited significant morbidity.

Main Outcome Measures  Tumorigenicity, extent of tumor invasion and metastasis, cell invasion and migration, and median survival.

Results  All the BRAF-mutated cell lines and 1 selected RET/PTC1–rearranged cell line were 100% tumorigenic in mice. These mouse tumor models exhibited a wide range of biological potential, including laryngeal invasion, lymph node metastasis, and pulmonary metastasis, thus reflecting the clinical spectrum of papillary carcinoma.

Conclusions  An orthotopic model of papillary thyroid carcinoma was successfully established in nude mice using BRAF-mutated and RET/PTC1–rearranged cell lines. These models mimic the human disease and will thus be useful for evaluating the clinical potential of novel targeted therapies.

Author Affiliations: Department of Head and Neck Surgery, The University of Texas M. D. Anderson Cancer Center, Houston.

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