The tight relationship between papillary thyroid cancer, autoimmunity and inflammation: Clinical and molecular studies

Marina Muzza, Debora Degl'Innocenti, Carla Colombo, Michela Perrino, Elena Ravasi, Stefania Rossi, Valentina Cirello, Paolo Beck-Peccoz, Maria Grazia Borrello, Laura Fugazzola

Research output: Contribution to journalArticle

Abstract

Objective The recent concept that oncogenes responsible for thyroid neoplastic transformation are able to elicit an inflammatory protumourigenic microenvironment raises interest in further studies on papillary thyroid cancer (PTC) associated with thyroid autoimmunity. Patients The clinical and molecular features, and the expression of inflammation-related genes, were investigated in a large series of PTCs with and without associated thyroiditis (groups A, n = 128 and B, n = 215). Results The two groups did not show significant differences in clinical and prognostic features, whereas they harboured a significantly different genetic background (P = 0·001), with RET/PTC1 being more represented in PTCs associated with autoimmunity, and BRAFV600E in patients with PTC alone. A RET/PTC rearrangement was also found in 41% of non-neoplastic thyroiditis tissues, contralateral to tumours harbouring either RET/PTC or BRAF mutations. The expression of genes encoding CCL20, CXCL8 and l-selectin was significantly higher in PTC specimens (either with RET/PTC, BRAFV600E or unknown genetic lesion) compared with normal thyroid samples. On the contrary, thyroiditis showed l-selectin expression levels even higher than PTCs, but CCL20 and CXCL8 levels comparable with normal tissues. Conclusions The present data extend the knowledge about the tight relationships among oncogenes, thyroiditis and thyroid cancer. A different genetic background among PTCs with and without associated autoimmunity has been firstly demonstrated. The strong association between RET/PTC1 and thyroiditis points to a critical role of this oncoprotein in the modulation of the autoimmune response. Moreover, preliminary expression studies, indicating enhanced expression of inflammatory molecules in PTCs, suggest a proinflammatory, nonautoimmune relationship between thyroiditis and thyroid cancer.

Original languageEnglish
Pages (from-to)702-708
Number of pages7
JournalClinical Endocrinology
Volume72
Issue number5
DOIs
Publication statusPublished - May 2010

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Thyroiditis
Factor IX
Autoimmunity
Inflammation
Selectins
Thyroid Gland
Oncogenes
Thyroid Neoplasms
Oncogene Proteins
Papillary Thyroid cancer
Clinical Studies
Gene Expression
Mutation
Genes
Neoplasms

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism

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The tight relationship between papillary thyroid cancer, autoimmunity and inflammation : Clinical and molecular studies. / Muzza, Marina; Degl'Innocenti, Debora; Colombo, Carla; Perrino, Michela; Ravasi, Elena; Rossi, Stefania; Cirello, Valentina; Beck-Peccoz, Paolo; Borrello, Maria Grazia; Fugazzola, Laura.

In: Clinical Endocrinology, Vol. 72, No. 5, 05.2010, p. 702-708.

Research output: Contribution to journalArticle

Muzza, Marina ; Degl'Innocenti, Debora ; Colombo, Carla ; Perrino, Michela ; Ravasi, Elena ; Rossi, Stefania ; Cirello, Valentina ; Beck-Peccoz, Paolo ; Borrello, Maria Grazia ; Fugazzola, Laura. / The tight relationship between papillary thyroid cancer, autoimmunity and inflammation : Clinical and molecular studies. In: Clinical Endocrinology. 2010 ; Vol. 72, No. 5. pp. 702-708.
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AU - Rossi, Stefania

AU - Cirello, Valentina

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AB - Objective The recent concept that oncogenes responsible for thyroid neoplastic transformation are able to elicit an inflammatory protumourigenic microenvironment raises interest in further studies on papillary thyroid cancer (PTC) associated with thyroid autoimmunity. Patients The clinical and molecular features, and the expression of inflammation-related genes, were investigated in a large series of PTCs with and without associated thyroiditis (groups A, n = 128 and B, n = 215). Results The two groups did not show significant differences in clinical and prognostic features, whereas they harboured a significantly different genetic background (P = 0·001), with RET/PTC1 being more represented in PTCs associated with autoimmunity, and BRAFV600E in patients with PTC alone. A RET/PTC rearrangement was also found in 41% of non-neoplastic thyroiditis tissues, contralateral to tumours harbouring either RET/PTC or BRAF mutations. The expression of genes encoding CCL20, CXCL8 and l-selectin was significantly higher in PTC specimens (either with RET/PTC, BRAFV600E or unknown genetic lesion) compared with normal thyroid samples. On the contrary, thyroiditis showed l-selectin expression levels even higher than PTCs, but CCL20 and CXCL8 levels comparable with normal tissues. Conclusions The present data extend the knowledge about the tight relationships among oncogenes, thyroiditis and thyroid cancer. A different genetic background among PTCs with and without associated autoimmunity has been firstly demonstrated. The strong association between RET/PTC1 and thyroiditis points to a critical role of this oncoprotein in the modulation of the autoimmune response. Moreover, preliminary expression studies, indicating enhanced expression of inflammatory molecules in PTCs, suggest a proinflammatory, nonautoimmune relationship between thyroiditis and thyroid cancer.

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