Familial Follicular Cell-Derived Thyroid Carcinoma

Son, Eun Ju; Nosé, Vânia

doi:10.3389/fendo.2012.00061

Cited by 24 publications

(27 citation statements)

References 46 publications

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“…Although a high percentage of apparently sporadic PCC/PGL cases is causatively linked to germline mutations (1), this is not the case for other tumor types. In particular, only 5-8% of RCCs, 5% of follicular cell-derived welldifferentiated thyroid cancers, !5% of PAs, 1-2% of testicular germ cell tumors, and NBLs respectively are familial when compared with 30-35% of PCCs/PGLs (1,24,63,64,65,66). With regard to the adenomatoid tumors, there is not only lack of any association with syndromic or genetic conditions but also no example of a typical two-hit mechanisms of TSG inactivation (12).…”

Section: Discussionmentioning

confidence: 99%

Non-pheochromocytoma (PCC)/paraganglioma (PGL) tumors in patients with succinate dehydrogenase-related PCC–PGL syndromes: a clinicopathological and molecular analysis

Papathomas

Gaal

Corssmit

et al. 2014

European Journal of Endocrinology

120

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Objective: Although the succinate dehydrogenase (SDH)-related tumor spectrum has been recently expanded, there are only rare reports of non-pheochromocytoma/paraganglioma tumors in SDHx-mutated patients. Therefore, questions still remain unresolved concerning the aforementioned tumors with regard to their pathogenesis, clinicopathological phenotype, and even causal relatedness to SDHx mutations. Absence of SDHB expression in tumors derived from tissues susceptible to SDH deficiency is not fully elucidated. Design and methods: Three unrelated SDHD patients, two with pituitary adenoma (PA) and one with papillary thyroid carcinoma (PTC), and three SDHB patients affected by renal cell carcinomas (RCCs) were identified from four European centers. SDHA/SDHB immunohistochemistry (IHC), SDHx mutation analysis, and loss of heterozygosity analysis of the involved SDHx gene were performed on all tumors. A cohort of 348 tumors of unknown SDHx mutational status, including renal tumors, PTCs, PAs, neuroblastic tumors, seminomas, and adenomatoid tumors, was investigated by SDHB IHC. Printed in Great BritainPublished by Bioscientifica Ltd.Conclusions: These findings strengthen the etiological association of SDHx genes with pituitary neoplasia and provide evidence against a link between PTC and SDHx mutations. Somatic deletions seem to constitute the second hit in SDHB-related renal neoplasia, while SDHx alterations do not appear to be primary drivers in sporadic tumorigenesis from tissues affected by SDH deficiency.

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Section: Discussionmentioning

confidence: 99%

Non-pheochromocytoma (PCC)/paraganglioma (PGL) tumors in patients with succinate dehydrogenase-related PCC–PGL syndromes: a clinicopathological and molecular analysis

Papathomas

Gaal

Corssmit

et al. 2014

European Journal of Endocrinology

120

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“…Furthermore, routine US screening may also identify incidental findings, such as ectopic thymus, that may confuse the clinical picture and potentially lead to unnecessary testing (75). A variety of genetic disorders predispose to thyroid neoplasia (85,86) (Table 4). Benign and malignant thyroid tumors can occur in patients with APC-associated polyposis (87), the Carney complex (88), the DICER1 syndrome (89,90), the PTEN hamartoma tumor syndrome (91)(92)(93), and Werner syndrome (94).…”

Section: In Children With Dtcmentioning

confidence: 99%

Management Guidelines for Children with Thyroid Nodules and Differentiated Thyroid Cancer

Francis

Waguespack

Bauer

et al. 2015

Thyroid

1,013

1,365

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Background: Previous guidelines for the management of thyroid nodules and cancers were geared toward adults. Compared with thyroid neoplasms in adults, however, those in the pediatric population exhibit differences in pathophysiology, clinical presentation, and long-term outcomes. Furthermore, therapy that may be recommended for an adult may not be appropriate for a child who is at low risk for death but at higher risk for long-term harm from overly aggressive treatment. For these reasons, unique guidelines for children and adolescents with thyroid tumors are needed. Methods: A task force commissioned by the American Thyroid Association (ATA) developed a series of clinically relevant questions pertaining to the management of children with thyroid nodules and differentiated thyroid cancer (DTC). Using an extensive literature search, primarily focused on studies that included subjects £ 18 years of age, the task force identified and reviewed relevant articles through April 2014. Recommendations were made based upon scientific evidence and expert opinion and were graded using a modified schema from the United States Preventive Services Task Force. Results: These inaugural guidelines provide recommendations for the evaluation and management of thyroid nodules in children and adolescents, including the role and interpretation of ultrasound, fine-needle aspiration cytology, and the management of benign nodules. Recommendations for the evaluation, treatment, and follow-up of children and adolescents with DTC are outlined and include preoperative staging, surgical management, postoperative staging, the role of radioactive iodine therapy, and goals for thyrotropin suppression. Management algorithms are proposed and separate recommendations for papillary and follicular thyroid cancers are provided.

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“…In addition to MAPK signaling, the importance of the PI3K/Akt signaling pathway in thyroid tumorigenesis has also been acknowledged [3]. Germline mutations that result in loss of PTEN , a negative regulator of PI3K signaling, predisposes for the development of FTC in humans [4]. Further, in addition to activation of the MAPK signaling pathway, RAS can also activate the PI3K pathway.…”

Section: Introductionmentioning

confidence: 99%

Immune Suppression Mediated by Myeloid and Lymphoid Derived Immune Cells in the Tumor Microenvironment Facilitates Progression of Thyroid Cancers Driven by HrasG12V and Pten Loss

Jolly¹,

Massoll²,

Franco³

2016

J Clin Cell Immunol

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Thyroid cancer is the most common endocrine malignancy and is predicted to be the 4th most commonly diagnosed cancer by 2030. Approximately one-half of follicular thyroid carcinomas (FTC) contain genetic alterations in RAS family members. Furthermore, Cowden's disease, which is characterized by loss of PTEN, predisposes for the development of FTC in humans. We have shown that thyroid specific expression of HrasG12V at endogenous levels and Pten inactivation (HrasG12V/Pten−/−/TPO-cre mice) leads to the development of FTCs that closely recapitulate human disease, with complete penetrance at one year. In patients, FTCs metastasize via the bloodstream to distant sites, frequently the lungs, bones and brain. The first objective of the study was to determine if these mice developed de novo metastasis to relevant sites. Indeed, spontaneous metastasis to the lungs was observed in 56% of HrasG12V/Pten−/−/TPO-cre mice. We next sought to identify the cellular components within the tumor microenvironment (TME) of FTC that contribute to tumor progression and metastasis via FACS analysis. Surprisingly, a large amount of immune infiltrate was observed. HrasG12V/Pten−/−/TPO-Cre thyroid tumors were comprised of 68.5 ± 11.79% CD45+ cells, in stark contrast to wild-type (WT) thyroids which were comprised of 17.6% CD45+ cells. Further, 53.1 ± 10.9% of the CD45+ cells from HrasG12V/Pten−/−/TPO-Cre thyroid tumors were of myeloid-lineage (CD11b+), consisting of macrophages (F4/80+Gr-1−) and myeloid-derived suppressor cells (F4/80−Gr-1+). Further, HrasG12V/Pten−/−/TPO-cre tumors contained Arginase-1 positive cells as determined by immunohistochemical analysis, supporting an immunosuppressive TME in HrasG12V/Pten−/−/TPO-Cre thyroid tumors. We next evaluated whether or not cytotoxic (CD8+) or helper T cells (CD4+) were recruited to HrasG12V/Pten−/−/TPO-Cre tumors. The majority of T cells in these tumors were double positive for CD4 and CD25, markers of immune suppressive regulatory T cells (Treg). Additionally, we identified Foxp3 positive cells by immunohistochemical analysis of tumor sections, indicating a functional suppressive Treg phenotype in vivo. HrasG12V/Pten−/−/TPO-Cre tumor cell lines displayed increased secretion of SDF-1, I-TAC, CCL9/10, and MCP5, cytokines that have been reported to play a direct role in the chemotaxis of immune cells and thus could contribute to the increased recruitment of myeloid and lymphoid derived cells in HrasG12V/Pten−/−/TPO-Cre tumors. These studies are the first to identify and implicate the interaction between tumor cells and immune cells in Ras-driven thyroid cancer progression, which we hope will lead to the development of more effective therapeutic approaches for aggressive forms of thyroid cancer that target the TME.

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Familial Follicular Cell-Derived Thyroid Carcinoma

Cited by 24 publications

References 46 publications

Non-pheochromocytoma (PCC)/paraganglioma (PGL) tumors in patients with succinate dehydrogenase-related PCC–PGL syndromes: a clinicopathological and molecular analysis

Non-pheochromocytoma (PCC)/paraganglioma (PGL) tumors in patients with succinate dehydrogenase-related PCC–PGL syndromes: a clinicopathological and molecular analysis

Management Guidelines for Children with Thyroid Nodules and Differentiated Thyroid Cancer

Immune Suppression Mediated by Myeloid and Lymphoid Derived Immune Cells in the Tumor Microenvironment Facilitates Progression of Thyroid Cancers Driven by HrasG12V and Pten Loss

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