Papillary thyroid carcinoma: 6 cases from 2 families with associated lymphocytic thyroiditis harbouring RET/PTC rearrangements

Mechler, Charlotte; Bounacer, Ali; Suárez, H. G.; Frison, M.; Magois, C; Aillet, G.; Gaulier, A

doi:10.1054/bjoc.2001.2187

Cited by 40 publications

(22 citation statements)

References 29 publications

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“…Indeed, RET/PTC expression was more likely to be found in occult or microcarcinomas of the thyroid than in poorly differentiated thyroid carcinomas, suggesting that RET/PTC activation is an early event in thyroid transformation (Viglietto et al, 1995;Bongarzone et al, 1996;Sugg et al, 1998;Fusco et al, 2002). Interestingly, RET/PTC expression has been frequently observed in patients afflicted with papillary thyroid carcinomas associated with autoimmune thyroiditis (Wirtschafter et al, 1997;Di Pasquale et al, 2001;Mechler et al, 2001) and in those patients with autoimmune thyroiditis but no pathologically detectable carcinoma (Wirtschafter et al, 1997;Sheils et al, 2000). Furthermore, patients diagnosed with autoimmune thyroiditis stained for c-RET protein, indicating that these specimens may express either an oncogenic RET/PTC family member or the protooncogene, c-RET, in thyroid epithelial cells (Di Pasquale et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

Tyrosine kinase oncoprotein, RET/PTC3, induces the secretion of myeloid growth and chemotactic factors

et al. 2003

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Differentiated thyroid carcinomas are the most frequent endocrine neoplasms, but account for few cancer-related deaths. Although the indolent growth of these cancers correlates well with longevity, the biological basis for this good prognosis is not known. In contrast, two of the most frequent autoimmune diseases involve the thyroid suggesting a high propensity for this organ to invoke destructive immunity. Unfortunately, the mechanism linking malignancy and autoimmunity is not clear, although the expression of the oncogenic fusion protein RET/PTC3 (RP3) in both of these disorders may provide a clue. Interestingly, the signaling caused by activated RET kinase involves overlapping pathways and some common to the inflammatory response. Accordingly, we analyzed the function of RP3 and a mutant RP3 molecule to induce proinflammatory pathways in thyroid epithelial cells. Indeed, we find that RP3 alone causes increases in nuclear NF-jB activity and secretion of MCP-1 and GM-CSF. Finally, transfer of RP3-expressing thyrocytes into mice in vivo attracted dense macrophage infiltrates, which lead to rapid thyroid cell death. Further, cytokine synthesis and inflammation was largely abrogated by mutation of RP3 Tyr 588 ; an important protein-binding site for downstream signaling. Together, these studies implicate oncogeneinduced cytokine-signaling pathways in a new mechanism linking inflammation with cancer.

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Section: Introductionmentioning

confidence: 99%

Tyrosine kinase oncoprotein, RET/PTC3, induces the secretion of myeloid growth and chemotactic factors

et al. 2003

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“…RET/ PTC oncogenes are a family of fusion proteins derived from chromosomal rearrangements involving the tyrosine kinase domain of the c-RET proto-oncogene and are frequent mutations found early in the development of a variety of differentiated thyroid carcinomas (Jhiang et al, 1992;Santoro et al, 1992;Fusco et al, 1995;Takahashi et al, 1995;Fugazzola et al, 1996;Sugg et al, 1996;Bongarzone et al, 1997). Whereas RET/PTC expression has been frequently observed in patients affected with PTCs showing concurrent thyroiditis, its expression was also reported in thyroid tissue of patients afflicted with HT with no detectable cancer suggesting a common etiology of these two diseases (Wirtschafter et al, 1997;Sheils et al, 2000;Mechler et al, 2001;Pasquale et al, 2001). The association of RET/PTC with HT suggested that oncoproteins may be one component involved in promoting organ-specific inflammation.…”

Section: Introductionmentioning

confidence: 99%

Interleukin 24 is induced by the RET/PTC3 oncoprotein and is an autocrine growth factor for epithelial cells

Shinohara

Rothstein

2004

Oncogene

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Thyroid cancers, like hematological malignancies, are commonly associated with chromosomal translocations leading to the formation of fusion proteins. Through altered signaling by fusion proteins, cell death and survival pathways are disrupted and the physiological balance of cell-cell communication may be lost. A consequence of this disruption is the release of factors by stressed cells that alert the host. One type of host response is leukocytic infiltration that may develop into chronic inflammation or autoimmune disease. Although inflammation can be associated with neoplastic tissue, the mechanism driving this process is largely unknown. Therefore, to address the mechanism of cancer inflammation we investigated the effects of an oncogene in a murine model system. A comprehensive genetic analysis revealed several soluble factors that were induced by RET/papillary thyroid carcinoma (PTC)3 gene expression including several proinflammatory cytokines, chemokines and immunologically relevant costimulatory molecules. Following a large genetic screen using RP3-expressing thyroid cells, we identified a highly abundant transcript and later identified it as interleukin 24 (Il24), a cytokine with diverse tumor suppressor and inflammatory activities. We show that RET/PTC3 induces Il24 expression in rat thyrocytes and that this expression is dependent on the signaling properties of its tyrosine kinase. Likewise, RET/PTC3 induces large amounts of Il24 following expression in murine thyrocytes, but its expression is dramatically reduced in poorly differentiated carcinomas, a finding that parallels the loss of RET/PTC3 expression. Consistent with its behavior as a tumor suppressor, the loss of Il24 coincided with the loss of RET/PTC3 in poorly differentiated mouse tumors. A functional role of Il24 in the autocrine growth/survival of RET/PTC3-expressing thyroid cells was identified helping to support its role in cellular transformation. These data suggest that the induction of Il24 by oncogenes may support tumor growth at the early stages of cancer.

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“…The possible association between Hashimoto's thyroiditis (HT) and papillary thyroid carcinoma (PTC) remains controversial. The association between HT and PTC is also supported by the observation that rearrangements of the rearranged during transfection (RET) oncogene is frequently detected in PTC (9).…”

Section: Introductionmentioning

confidence: 84%

Hashimoto's thyroiditis and papillary carcinoma in an adolescent girl: A case report

Dong

Sun

Cheng

et al. 2016

Molecular and Clinical Oncology

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Abstract. Hashimoto's thyroiditis with thyroid cancer in childhood is not as common in the adult population. Hashimoto's thyroiditis is an autoimmune disease associated with autoantibodies, and the association between Hashimoto's thyroiditis and papillary carcinoma of the thyroid remains controversial. The present study reported a 15-year-old adolescent girl with the diagnosis of Hashimoto's thyroiditis with thyroid cancer. With the complexity of the clinical manifestations of Hashimoto's thyroiditis, it can be expressed as not only hyperthyroidism or hypothyroidism, but also normal thyroid function. The long-term treatment, and for children with thyroid cancer, early diagnosis is particularly difficult. In the present case, the diagnosis of Hashimoto's thyroiditis is primarily based on clinical manifestations, anti-thyroglobulin antibody and anti-thyroid microsomal antibody. The only diagnostic imaging ultrasound was negative. The present study discussed the possible reason and the identification of this unique case of Hashimoto's thyroiditis with thyroid cancer. IntroductionHashimoto's thyroiditis is autoimmune thyroid disease in children. The most principal locations of pediatric thyroid disease is in iodine-sufficient areas worldwide (1). At the time of diagnosis, thyroid function of children and adolescent with Hashimoto's thyroiditis may significantly vary in the different pediatric reports, ranging from euthyroidism to overt hypothyroidism or occasionally, hyperthyroidism (2-7). Epidemiological data showed that thyroid cancer frequently occurs in the context of one of the most common autoimmune thyroid diseases, Hashimoto's thyroiditis (8). The possible association between Hashimoto's thyroiditis (HT) and papillary thyroid carcinoma (PTC) remains controversial. The association between HT and PTC is also supported by the observation that rearrangements of the rearranged during transfection (RET) oncogene is frequently detected in PTC (9). Case reportA 15-year-old adolescent girl was admitted to a local hospital and a left neck mass (~1.0x1.5 cm 2 ) was found one year ago. The mass was not accompanied by pain, itching, chills, fever and cough; however, the girl did experienced weight loss, heat intolerance and sweating. The patient had taken Chinese herbal medicine, however this had no effect. She visited a local hospital for treatment 9 months ago. Physical examination revealed the painless left goiter ~1.5x1.5 cm 2 , without vascular murmur. Laboratory examination results revealed normal thyroid function, anti-thyroglobulin antibody (TG-Ab) of 52.35% (<30%) and anti-thyroid microsomal antibody (TM-Ab) of 37.01% (<20%). The neck ultrasound examination revealed no thyroid lesions. It was diagnosed as Hashimoto's thyroiditis. After 3 months of observation, the neck mass had grown. The neck ultrasound examination revealed that a left lobe of the thyroid exhibited multiple solid hypoechoic nodules and calcification to the left neck lymph nodes. The right thyroid lobe and isthmus were normal. A lymph node biops...

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Papillary thyroid carcinoma: 6 cases from 2 families with associated lymphocytic thyroiditis harbouring RET/PTC rearrangements

Cited by 40 publications

References 29 publications

Tyrosine kinase oncoprotein, RET/PTC3, induces the secretion of myeloid growth and chemotactic factors

Tyrosine kinase oncoprotein, RET/PTC3, induces the secretion of myeloid growth and chemotactic factors

Interleukin 24 is induced by the RET/PTC3 oncoprotein and is an autocrine growth factor for epithelial cells

Hashimoto's thyroiditis and papillary carcinoma in an adolescent girl: A case report

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