The Association Between Chronic Lymphocytic Thyroiditis and Thyroid Tumors

Tamimi, Dalal M. Al

doi:10.1177/106689690201000207

Cited by 117 publications

(87 citation statements)

References 16 publications

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“…RET/PTC fusion proteins, like RP3, may be directly responsible for provoking the chronic inflammatory disease coincident with cancer in thyroid disease patients. This is of particular interest since the frequency of thyroiditis in thyroid cancer is approximately 30% (Braverman and Utiger, 1995;Kebebew et al, 2001) and can be as high as 50% in some patients (Tamimi, 2002). Furthermore, thyroiditis may become a common malady as we age, since an estimated 6.6% of autopsies show pathological evidence of thyroiditis in normal (euthyroid) individuals (Fleischmann and Hardmeier, 1999).…”

Section: Discussionmentioning

confidence: 99%

“…This association was shown to correspond to a favorable clinical outcome in patients with infrequent tumor recurrence, more differentiated tumors and lower mortality rates (Matsubayashi et al, 1995;Loh et al, 1999;Tamimi, 2002). While the origins of papillary thyroid carcinoma-associated lymphocytic thyroiditis are unknown, genetic analysis of papillary thyroid carcinomas has shown that specific chromosomal rearrangements of the RET/PTC gene family are prevalent (Jhiang, 2000).…”

Section: Introductionmentioning

confidence: 99%

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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: Discussionmentioning

confidence: 99%

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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“…Consistent with this notion, 10-40% of patients diagnosed with Hashimoto's thyroiditis (HT) may show evidence of concurrent thyroid carcinoma (Dailey et al, 1955;Ott et al, 1987). Although the role of these immune infiltrates is uncertain, clinical studies have shown that patients with papillary thyroid carcinoma (PTC) that present with thyroiditis (PTC/ HT) have a better clinical outcome than patients diagnosed with PTC alone (Matsubayashi et al, 1995;Loh et al, 1999;Tamimi, 2002). Understanding the molecular mechanisms that distinguish PTC from PTC/ HT will be critical if we are to take advantage of the anticancer responses that likely explain the difference between these two pathologies.…”

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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“…From a histological perspective, Tamimi et al assessed the prevalence and severity of thyroiditis among three types of surgically resected thyroid tumors and found a significantly higher rate of lymphocytic infiltrate in patients with PTC [14]. Again PTC with concurrent HT is associated with female gender, young age, less aggressive disease such as small tumor size, less frequent capsular invasion and nodal metastasis, and better prognosis [15,16].…”

Section: Hashimoto's Thyroiditis and Papillary Thyroid Cancermentioning

confidence: 99%

“…Again PTC with concurrent HT is associated with female gender, young age, less aggressive disease such as small tumor size, less frequent capsular invasion and nodal metastasis, and better prognosis [15,16]. Furthermore, these patients are also less likely to develop recurrence and have a higher survival rate [14,15,17,18], mostly explained by the fact that the autoimmune response to thyroid specific antigens in patients with HT may be involved in the destruction of cancer cells expressing thyroid specific antigen in PTC. However, it remains unclear whether or not the presence of HT affects the biologic behavior of PTC, although the association between HT and PTC has been reported in many studies [9,15,18,23].…”

Section: Hashimoto's Thyroiditis and Papillary Thyroid Cancermentioning

confidence: 99%

Hashimoto’s Thyroiditis And Cancer: A Review

Salti

2017

int arch med

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Background: No consensus exists on the association betweenHashimoto's thyroiditis (HT) and cancer. To resolve this controversy, this review aimed to evaluate the relationship between the two conditions. Methods:Using pub-med database, we searched studies relevant to the topic focusing on the association between HT and papillary thyroid cancer (PTC), as well as the association between HT and primary thyroid lymphoma (PTL).Findings: Both HT and PTC are common worldwide, and the two conditions may be closely related. However, the relationship remains controversial. Some studies found that PTC coexisted with HT 2.8-fold more frequently, with variable prevalence ranging from 0.5 to 30%. In contrast to surgical and pathological series that suggested a positive correlation between the two diseases and even a cause-and-effect relationship, the other studies evaluating fine-needle aspirate specimens did not find a statistically significant correlation. On the other hand, the relationship between PTL and HT appears well established. Conclusion:The existing data provide inconsistent evidence favoring a causal relationship between HT and PTC. Prospective studies are needed to further elucidate the relationship. However patients with HT are at risk for PTL. Therefore careful observation and follow-up of HT patients is recommended.

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The Association Between Chronic Lymphocytic Thyroiditis and Thyroid Tumors

Cited by 117 publications

References 16 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 Cancer: A Review

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