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 center dot 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.

The tight relationship between papillary thyroid cancer, autoimmunity and inflammation : clinical and molecular studies / M. Muzza, D. Degl'Innocenti, C. Colombo, M. Perrino, E. Ravasi, S. Rossi, V. Cirello, P.L.M. Beck Peccoz, M.G. Borrello, L. Fugazzola. - In: CLINICAL ENDOCRINOLOGY. - ISSN 0300-0664. - 72:5(2010 May), pp. 702-708. [10.1111/j.1365-2265.2009.03699.x]

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

M. Muzza;C. Colombo;M. Perrino;V. Cirello;P.L.M. Beck Peccoz;L. Fugazzola
2010

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 center dot 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.
Settore MED/13 - Endocrinologia
mag-2010
Article (author)
File in questo prodotto:
Non ci sono file associati a questo prodotto.
Pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/155409
Citazioni
  • ???jsp.display-item.citation.pmc??? 50
  • Scopus 148
  • ???jsp.display-item.citation.isi??? 128
social impact