A mouse model of BRAF V600E mutated papillary thyroid cancer imitating sporadic conditions

2018 ◽  
Author(s):  
Iva Jakubikova ◽  
Elin Schoultz ◽  
Ellen Johansson ◽  
Shawn Liang ◽  
Konrad Patyra ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Mouse Model ◽  
Papillary Thyroid Cancer ◽  
Braf V600e ◽  
Papillary Thyroid

scholarly journals Pre-existing thyroiditis ameliorates papillary thyroid cancer: insights from a new mouse model

Endocrinology ◽  
2021 ◽  
Author(s):  
Fabiana Pani ◽  
Yoshinori Yasuda ◽  
Giulia Di Dalmazi ◽  
Paulina Chalan ◽  
Kathleen Gabrielson ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Mouse Model ◽  
Papillary Thyroid Cancer ◽  
Braf V600e ◽  
Effector Memory ◽  
Papillary Thyroid ◽  
Mononuclear Cell Infiltration ◽  
Memory Cd8 T Cells ◽  
Chi Squared ◽  
Shed Light

Abstract 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.

scholarly journals Epigenetically upregulated WIPF1 plays a major role in BRAF V600E-promoted papillary thyroid cancer aggressiveness

Oncotarget ◽  
2016 ◽  
Vol 8 (1) ◽  
pp. 900-914 ◽  
Author(s):  
Tao Zhang ◽  
Xiaopei Shen ◽  
Rengyun Liu ◽  
Guangwu Zhu ◽  
Justin Bishop ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Papillary Thyroid Cancer ◽  
Braf V600e ◽  
Papillary Thyroid ◽  
Cancer Aggressiveness

scholarly journals Correlation between F18-FDG PET/CT Imaging and BRAF V600E Genetic Mutation for the Early Assessment of Treatment Response in Papillary Thyroid Cancers

2020 ◽  
Vol 10 (2) ◽  
pp. 52
Author(s):  
Andra Piciu ◽  
Maria-Iulia Larg ◽  
Doina Piciu
Keyword(s):  
Thyroid Cancer ◽  
Prognostic Factors ◽  
Papillary Thyroid Cancer ◽  
Genetic Mutation ◽  
Braf V600e Mutation ◽  
Braf V600e ◽  
Papillary Thyroid ◽  
Early Assessment ◽  
Pet Ct ◽  
Ct Evaluation

In thyroid neoplastic pathology, the BRAF V600E mutation is shown to be involved in the oncogenesis of papillary thyroid cancer and its subtypes. The purpose of this study is to evaluate the correlation between the mutation of the BRAF V600E oncogene and the pathological standardized uptake values (SUV) at the F18-fluorodeoxyglucose (F18-FDG) positron emission tomography/computed tomography (PET/CT) evaluation, for a group of 20 patients with radically treated (total thyroidectomy and radioiodine therapy) papillary thyroid cancer, with subclinical persistent disease, at 6 months after the initial treatment. We analyzed the correlations between the values of SUV and the presence of the BRAF mutation as well with other prognostic factors such as stage, age, specific tumor markers (thyroglobulin and anti-thyroglobulin), extrathyroid extension, the presence of metastatic lymph nodes or distant metastasis. The value of SUV in the case of BRAF+ (positive) patients was higher than in the negative ones, but without statistical significance, thus, the values of the SUV cannot be a predictable factor for the presence of the genetic mutation. There was a statistically significant correlation in BRAF+ subgroup between the SUV values and the positive resection limit following surgery, showing a higher SUV value in the PET/CT evaluation. No correlation was observed between the aforementioned prognostic factors involved in papillary thyroid cancer and the BRAF V600E mutation.

scholarly journals The BRAF V600E mutation is a predictor of the effect of radioiodine therapy in papillary thyroid cancer

2020 ◽  
Vol 11 (4) ◽  
pp. 932-939 ◽  
Author(s):  
Junshang Ge ◽  
Jie Wang ◽  
Hui Wang ◽  
Xianjie Jiang ◽  
Qianjin Liao ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Papillary Thyroid Cancer ◽  
Radioiodine Therapy ◽  
Braf V600e Mutation ◽  
Braf V600e ◽  
Papillary Thyroid

scholarly journals Redifferentiation of Iodine-Refractory BRAF V600E-Mutant Metastatic Papillary Thyroid Cancer with Dabrafenib—Response

2015 ◽  
Vol 21 (24) ◽  
pp. 5640-5641 ◽  
Author(s):  
S. Michael Rothenberg ◽  
Gilbert H. Daniels ◽  
Lori J. Wirth
Keyword(s):  
Thyroid Cancer ◽  
Papillary Thyroid Cancer ◽  
Braf V600e ◽  
Papillary Thyroid

BRAF V600E Mutation Independently Predicts Central Compartment Lymph Node Metastasis in Patients with Papillary Thyroid Cancer

2012 ◽  
Vol 20 (1) ◽  
pp. 47-52 ◽  
Author(s):  
Gina M. Howell ◽  
Marina N. Nikiforova ◽  
Sally E. Carty ◽  
Michaele J. Armstrong ◽  
Steven P. Hodak ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Lymph Node ◽  
Lymph Node Metastasis ◽  
Papillary Thyroid Cancer ◽  
Central Compartment ◽  
Braf V600e Mutation ◽  
Braf V600e ◽  
Papillary Thyroid ◽  
Node Metastasis

scholarly journals SUN-484 Complex Thyroid Cancer with Several Recurrences and Metastases

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Kruti K Patel ◽  
Michael Via
Keyword(s):  
Thyroid Cancer ◽  
Tyrosine Kinase ◽  
Disease Progression ◽  
Papillary Thyroid Cancer ◽  
Braf V600e ◽  
Whole Body ◽  
Papillary Thyroid ◽  
Whole Body Scan ◽  
Body Scan ◽  
Hilar Lymph Node

Abstract 56-year-old male with metastatic papillary thyroid cancer who underwent total thyroidectomy in 8/2014, and I-131 ablation in 9/2014, with post-operative pathology revealing multifocal, bilateral papillary thyroid cancer with extrathyroidal extension with surgical resection margins uninvolved. There were positive lymphovascular spread and multiple central compartments and bilateral neck nodes metastases with extranodal extension. Subsequent thyrogen stimulated whole-body scan in 2/2016 showed no areas of uptake.However, in 12/2016 he was found to have right supraclavicular lymph nodes positive for recurrence which was resected and given another 168 mCi I-131 and 33 treatments of XRT to R shoulder.A repeat PET in 7/2019 showed persistent hyper metabolic lesion in C7, multiple hyper metabolic nodules throughout the R lung, and a new 1.1 cm left Hilar lymph node suggesting disease progression. Biopsy of the C7 lesion confirmed dedifferentiated papillary thyroid cancer and demonstrated the presence of an NTRK mutation.This time he was given lenvatinib 24 mg daily for 4 weeks, followed by 200 mCi I-131. Post-treatment whole body scan showed good uptake in all lesions, except the C7 lesion which was treated with external radiation. DiscussionWhile cure is achieved in most cases of differentiated thyroid cancer, a minority of cases demonstrate disease progression. Loss of response to I-131, very low serum thyroglobulin levels despite known disease, and high PET avidity provide clinical evidence of dedifferentiation, confirmed with tissue sampling.If feasible targeted systemic therapy remains the best tolerated treatment option.While several studies demonstrate an increase in iodine avidity in approximately 50-60% of patients with dedifferentiated thyroid cancer that were treated with tyrosine kinase inhibitors (TKI), (cite alan Ho’s 2013 NEJM article, and the 2015 debrafenib study Rothenberg SM et al, clin cancer res 2015), selumetanib remains unavailable for clinical use and dabrafenib may only be beneficial in cases with known BRAF V600E mutations. Moreover, it is unknown whether a planned short course of TKI therapy would potentially induce resistance to future TKI therapy.Therefore, lenvatinib, which inhibits activity of at least 6[VM1] different tyrosine kinase enzymes important in thyroid cancer was chosen rather than entrectanib, which was reserved for use if the need arises. This patient demonstrated excellent response to I-131 therapy with lenvatinib pretreatment.A number of formal studies of various TKIs for thyroid cancer re-differentiation are currently underway. (cite Brown SR, Hall A, et al BMC cancer 2019; and also cite the CIII trial with cabozatanib)Conclusion This case represents the emerging paradigm for the ability of TKI therapy to redifferentiate advanced thyroid cancer and allow for re-treatment with I-131 targeted therapy.

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