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


METHODS
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 BRAF(V600E) 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, BRAF(V600E) 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.
Muzza
Marina
M
Department of Medical Sciences, University of Milan and Endocrine Unit, Fondazione Policlinico IRCCS, Milan.
Degl'Innocenti
Debora
D
Colombo
Carla
C
Perrino
Michela
M
Ravasi
Elena
E
Rossi
Stefania
S
Cirello
Valentina
V
Beck-Peccoz
Paolo
P
Borrello
Maria Grazia
MG
Fugazzola
Laura
L
D000293:Adolescent; D000328:Adult; D000368:Aged; D015551:Autoimmunity; D002291:Carcinoma, Papillary / Q000235:genetics / Q000473:pathology*; D054418:Chemokine CCL20 / Q000235:genetics; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000276:immunology / Q000473:pathology*; D016209:Interleukin-8 / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D011505:Protein-Tyrosine Kinases / Q000235:genetics; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013964:Thyroid Neoplasms / Q000235:genetics / Q000276:immunology / Q000473:pathology*; D013966:Thyroiditis / Q000235:genetics / Q000276:immunology / Q000473:pathology; D055815:Young Adult
D054418:Chemokine CCL20; D016209:Interleukin-8; D015514:Oncogene Proteins, Fusion; D011505:Protein-Tyrosine Kinases; C093573:ret-PTC fusion oncoproteins, human; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf