Aberrant sonic hedgehog signaling pathway and STAT3 activation in papillary thyroid cancer.

The sonic hedgehog (SHH) and STAT3 signaling pathways play important roles during carcinogenesis with possible interaction. To determine the association of the activation of SHH signaling pathway and STAT3 pathway in carcinogenesis of human papillary thyroid cancer (PTC), we examined the expression of SHH signaling pathway molecules including SHH, Patched (PTCH), Smoothened (SMO) and GLI1 (glioma-associated oncogene homolog 1), as well as p-STAT3 (phosphorylation at Tyr705) by immunohistochemistry in 164 cases of PTC. In PTC, 70.12%, 64.02%, 68.90%, 64.02%, and 56.71% and in the adjacent normal thyroid tissues, 18.29%, 18.90%, 26.83%, 14.63%, and 10.98% of the specimens stained positive for SHH, PTCH, SMO, GLI1, and p-STAT3, respectively. Significant difference were found for the positive rate of SHH, PTCH, SMO, and GLI1 as well as p-STAT3 expression between PTC and adjacent normal thyroid tissues. There was a high accordance rate between SHH, PTCH, SMO, and GLI1 expression and all of them positively correlated with larger tumor size, the presence of ETE and LNM, and higher TNM stage. P-STAT3 expression positively correlated with the presence of ETE and LNM, and higher TNM stage but not age, gender, tumor size of the PTC patients. Signifi cant positive correlation between p-STAT3 and SHH, PTCH, SMO and GLI expression was found in PTC. These findings suggest that the SHH and STAT3 signaling pathways are frequently activated in PTC, interact with each other and may therefore be indicators for prognosis or potential targets for therapy against PTC.