K. K. Rossfeld1, D. Huk2, S. E. Justiniano2, M. Saji2, L. A. Shirley1, M. D. Ringel2, L. S. Kirschner2, J. E. Phay1 1Ohio State University,Surgical Oncology,Columbus, OH, USA 2Ohio State University,Endocrinology, Diabetes, And Metabolism,Columbus, OH, USA
Introduction: Patients with locally aggressive and metastatic thyroid cancer have limited treatment options. Preclinical animal modeling is an important step in developing new therapies for these patients. Existing thyroid cancer mouse models promote tumor growth either through orthotopic injection of cancer cells or via genetic alterations. Unfortunately, tumor growth in the thyroid gland in these models often causes local compression or invasion requiring early euthanasia. We sought to determine whether surgical resection of the thyroid without the demise of the animal was feasible.
Methods: Mice with thyroid-specific deletion of Pten develop follicular adenomas, and mice with thyroid-specific deletion of Prkar1a develop follicular thyroid cancer (FTC). Mice with combination Pten and Prkar1a thyroid deletion develop vascular FTC; half develop pulmonary metastases. We have recently described a medullary thyroid cancer (MTC) orthotopic xenograft model. Five mice were selected for surgical resection, one with Pten deletion, one with Prkar1a deletion, and one with an MTC orthotopic xenograft, along with two mice with double Prkar1a/Pten deletion.
Results: Three of the five mice survived surgical resection of their tumors. The Pten knockout mouse survived 6 months postoperatively. The Prkar1a knockout mouse had a local recurrence and required euthanasia one month following surgical resection. The mouse with the MTC orthotopic xenograft survived resection but also developed local recurrence and required sacrifice after three months. Both Prkar1a/Pten knockout mice suffered perioperative mortality.?
Conclusion: Survival after surgical resection of a thyroid neoplasm in the murine model was demonstrated in three of four models. The mortalities seen in Prkar1a/Pten knockout mice were secondary to difficulty with vascular control as well as hyperthyroidism. Interestingly, local recurrence of the resected tumor was observed in two cancer models, which is often a clinical challenge in patients with thyroid cancer. These models may allow for further investigation of molecular mechanisms underlying local recurrence, novel surgical techniques, such as image-guided surgery, and novel chemotherapies for metastatic disease. ?