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.
Trovato
M
M
Department of Pathology, Policlinico Universitario, Messina, Italy.
Grosso
M
M
Vitarelli
E
E
Ruggeri
R M
RM
Alesci
S
S
Trimarchi
F
F
Barresi
G
G
Benvenga
S
S
D000236:Adenoma / Q000378:metabolism*; D002277:Carcinoma / Q000378:metabolism; D002291:Carcinoma, Papillary / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000096:biosynthesis*; D004847:Epithelial Cells / Q000378:metabolism; D017228:Hepatocyte Growth Factor / Q000096:biosynthesis; D006801:Humans; D007150:Immunohistochemistry; D015850:Interleukin-6 / Q000096:biosynthesis; D019859:Proto-Oncogene Proteins c-met / Q000096:biosynthesis; D019947:Receptors, Interleukin-6 / Q000096:biosynthesis; D050796:STAT3 Transcription Factor; D013961:Thyroid Gland / Q000187:drug effects / Q000378:metabolism; D013964:Thyroid Neoplasms / Q000378:metabolism*; D016606:Thyroid Nodule / Q000378:metabolism; D016610:Tissue Embedding; D015534:Trans-Activators / Q000096:biosynthesis*
D004268:DNA-Binding Proteins; D015850:Interleukin-6; D019947:Receptors, Interleukin-6; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D015534:Trans-Activators; D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met