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Publication : Pre-existing Thyroiditis Ameliorates Papillary Thyroid Cancer: Insights From a New Mouse Model.

First Author  Pani F Year  2021
Journal  Endocrinology Volume  162
Issue  10 PubMed ID  34331442
Mgi Jnum  J:309474 Mgi Id  MGI:6758611
Doi  10.1210/endocr/bqab144 Citation  Pani F, et al. (2021) Pre-existing thyroiditis ameliorates papillary thyroid cancer: insights from a new mouse model. Endocrinology 162(10)
abstractText  Papillary Thyroid Cancer (PTC) often co-occurs with Hashimoto's thyroiditis, an association that has long been reported in clinical studies yet remains controversial. Some studies, in fact, have suggested a protective effect of thyroiditis while others have not. We generated a mouse model where PTC and thyroiditis develop in a predictable manner, combining the oncogenic drive of the BRAF v600E mutation (inducible by tamoxifen) to the thyroiditis susceptibility of the NOD.H2 h4 strain (inducible by iodine). A total of 113 NOD.H2h4_TPO-CRE-ER_BRAFV600E mice (50 followed throughout lifetime and 63 sacrificed at 16 weeks post tamoxifen) were used to determine whether the PTC phenotype differs when thyroiditis precedes or coincides with the onset of PTC. Mice with pre-existing thyroiditis lived longer (median survival of 28.2 weeks post tamoxifen) than those with concomitant (25.6 weeks) or no (24.5 weeks) thyroiditis (p<0.01 by Laplace regression). PTC developed less frequently (33%) in the pre-existing thyroiditis group than the concomitant (100%) or no (100%) thyroiditis groups (p<0.001 by chi-squared) and showed less aggressive histopathological features. The intra-tumoral mononuclear cell infiltration was more prominent in mice with pre-existing thyroiditis (p= 0.002 versus the other groups) and sustained by a significant expansion of effector memory CD8+ T cells and CD19+ B cells. These findings shed light on the controversial PTC-thyroiditis association and emphasize the contribution of intra-tumoral T and B lymphocytes to the evolution of PTC.
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