Histopathological changes induced by selective inactivation of menin on the thyroid gland in RET÷PTC3 and E7 transgenic mice. A study of 77 cases.

Multiple Endocrine Neoplasia Type 1 (MEN1) does not involve the thyroid gland, but animal studies have shown that mice with inactivation of menin could develop thyroid pathologies. The objective was to evaluate if the selective inactivation of menin in murine thyroid glands expressing RET÷PTC3 and E7 oncogenes, might induce an increased index of proliferation and a more rapid development of thyroid hyperplasia and÷or tumors. The thyroid glands of 77 mice aged 4-18 months (31 expressing the E7 oncogene and 25 the RET÷PTC3 oncogene) were analyzed for histological changes and Ki67 proliferation index. Fifty-two mice had selective inactivation of menin in the thyroid gland (16 mice with RET÷PTC3 oncogene and 19 mice with E7 oncogene). As compared to wild type, mice with inactivation of menin presented an increased Ki67 proliferation index. Mice presenting the E7 oncogene showed larger thyroid glands with a pattern of diffuse hyperplasia. Mice expressing the RET÷PTC3 oncogene presented larger thyroid glands compared to the wild type mice but smaller compared to E7 mice. The lesions in the RET÷PTC3 group were "proliferative papillary cystic changes" (60%), "cribriform" (16%), "solid" (8%) and a combination of these patterns in the rest of the thyroid glands. The inactivation of menin in the thyroid gland of young mice does not seem to change the histological pattern, but it influences the proliferation of follicular cells. Further molecular studies especially in aged mice are needed to better understand the correlation between certain oncogenes and the inactive status of menin.