Growth and function of thirty-four human benign and malignant thyroid xenografts in untreated nude mice

Tissue was taken from 16 patients with benign thyroid lesions (10 nontoxic nodular colloid goiter, two follicular adenoma, one autonomous adenoma, one iodine-induced thyrotoxicosis, 2 Graves' disease) and 18 patients with malignant thyroid tumors [seven papillary, five follicular, five undifferentiated (anaplastic), and one medullalry carcinoma] and was xenotransplanted into the flanks of 124 syngeneic female BALB/c-nu/nu mice 6 weeks of age. Subsequently, without any further treatment, serum levels of thyroglobulin (TG), T3, T4, and thyroid-stimulating hormone were determined by radioimmunoassay at 4 or 5 weeks posttransplantation and at the end of the experimental time period of 4 months. All animals were autopsied. The grafts were examined by light microscopy and TG immunohistochemistry. Morphologically, the grafts of benign and malignant thyroid tumors showed features overall identical to the original tissue. Conversely, nontoxic nodular colloid goiter and Graves' disease grafts revealed a transformation to normofollicular structures. All benign thyroid grafts showed a stationary growth, as did most differentiated thyroid carcinomas. Tumor take rates in differentiated and in medullary carcinoma were 15%, and in undifferentiated carcinomas, 100%. In the cancer grafts, a correlation between resting phase (period until progressive tumor growth) and survival time of the corresponding patients was disclosed. All patients whose tumors were not taken by nude mice are still alive and show no signs of progressive tumor growth at 9 to 34 months after surgery. All but one patient with tumors revealing positive tumor take died within 3 months (resting phase, 3 weeks) or one year (resting phase, 7 to 14 weeks) after surgery. Integrity of hormonal function in benign and malignant xenografts at 4 months posttransplantation could be shown by significantly higher T3 and T4 serum concentrations in animals with benign thyroid tissues (T3, 1.69 +/- 0.13 nmol/liter; T4, 45.69 +/- 2.09 nmol/liter; S.E.) as compared to controls without grafted tissue [T3, 1.29 +/- 0.10 nmol/liter (p less than 0.05); T4, 33.39 +/- 2.71 nmol/liter (p less than 0.05)] and by increased TG serum concentrations in animals receiving benign (TG, 2.70 +/- 1.39 ng/ml) or malignant (e.g., TG in follicular carcinoma, 34.44 +/- 13.83 ng/ml; controls, 0.30 +/- 0.02 ng/ml) thyroid tissue. Thus, we conclude that benign and malignant thyroid xenografts in the nude mouse maintain full morphological and, regarding T3, T4, and TG serum levels, functional integrity for at least 4 months after transplantation.