The tyrosine kinase receptor c-met, its cognate ligand HGF and the tyrosine kinase receptor trasducers STAT3, PI3K and RHO in thyroid nodules associated with Hashimoto's thyroiditis: an immunohisto-chemical characterization

Hepatocyte growth factor (HGF) exerts proliferative activities in thyrocytes upon binding to its tyrosine kinase receptor c-met and is also expressed in benign thyroid nodules as well as in Hashimoto's thyroiditis (HT)

Immunoexpression of the CD30 ligand-CD30 and IL-6-IL-6R signals in thyroid autoimmune diseases

To elucidate the role of Th2 cytokines in autoimmune thyroid diseases, we have studied by immunohistochemistry the expression of two Th2 ligand/receptor systems (CD30-L/CD30 and IL-6/IL-6R) in goitrous Graves’ disease (GD) and Hashimoto’s thyroiditis (HT). A total number of 50 nodular goiters (NG), including 10 GD showing a lymphoid aggregate grade I, 30 HT 8 of which had a lymphoid aggregate of grade I, 12 of grade II and 10 grade III, and 10 colloid goiters have been evaluated. In addition, 5 normal thyroids were included in the study as controls. Reactivity of ligand and cognate receptor of both CD30-L/CD30 and IL-6/IL-6R pathways was observed in a greater proportion of GD, compared to HT (P<0.005). In HT, the expression of CD30-L/CD30 system was detected more frequently than IL-6/IL-6R (P<0.05) and showed an inverse correlation with the grade of lymphoid aggregate, whereas IL-6/IL-6R correlated positively with lymphocyte infiltration (P<0.05). Based on our results concerning a dominance of Th2 cytokines in GD, we postulate that CD30-L/CD30 and IL-6/IL-6R systems could play a major role in the pathogenesis of GD. However, the expression of CD30L/CD30 and IL-6/IL-6R in HT suggests that Th2 mechanisms are involved also in tissue damage of HT. The two systems could contribute to drive the autoimmune response skewing toward a Th2 phenotype and this appears to be correlated with the lymphoid aggregate grade

Distinctive expression of STAT3 in papillary thyroid carcinomas and a subset of follicular adenomas

Hepatocyte growth factor (HGF), HGF receptor (c-met) and the interleukin 6 (IL-6) are expressed in thyroid nodules. In extra-thyroidal tissues, the HGF/c-met and IL-6/IL-6 receptor (IL-6R) systems activate STAT3, a member of the signal transducers and activators of transcription (STATs) family. To evaluate whether either system utilizes STAT3 in thyroid nodules, we examined the immunohistochemical expression of HGF, c-met, IL-6, IL-6R, STAT3 in 6 normal thyroids and in 68 thyroid nodules. STAT3 expression was observed in 12/12 (100%) papillary thyroid carcinomas (PTC) but in none of the follicular tumors. Among benign thyroid nodules, only 2/10 (20%) follicular adenomas (FA) were STAT3+. All these 14 STAT3+ cases expressed both HGF and c-met, but only 5 PTC co-expressed IL-6 and IL-6R and the 2 FA were IL-6+ but IL-6R-. The remaining 8 FA were all HGF-/c-met-, but IL-6+; of these 8, only 2 were also IL- 6R+. In conclusion, in thyroid nodules STAT3 is expressed only in PTC and a number of FA. Since these cases are consistently HGF+/c-met+ and only one-third of them co-express IL-6/IL-6R, STAT3 expression correlates with the HGF/c-met expression, not with the IL-6/IL-6R expression. The 100% rate of expression of the HGF/c-met/STAT3 signaling in PTC could be relevant for the establishment of the papillary phenotype. Because of the communeness of a HGF/c-met/STAT3 pattern between all PTC and a subset of FA, we speculate that a fraction of FA may progress to PTC

Characteristics, management, and outcomes of patients with left‐sided infective endocarditis complicated by heart failure: a substudy of the ESC‐EORP EURO‐ENDO (European infective endocarditis) registry

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