Nuclear STAT3 expression is associated with favorable prognosis in papillary thyroid carcinoma.
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INTRODUCTION: Signal transducer and activator of transcription 3 (STAT3) is a signaling molecule that functions downstream of various cytokine and growth factor receptor signaling pathways to regulate cell growth, survival, and differentiation. Constitutive activation of STAT3 is relevant to cancer development and progression in many types of malignancies. In this study, the relationship between STAT3 activation and the prognosis of papillary thyroid carcinoma (PTC) was retrospectively examined using immunohistochemical staining with an anti-STAT3 antibody. MATERIALS AND METHODS: A total of 1,132 PTC cases with M0 diagnosed between 1993 and 2012 were included. The H-score (0-300 points) was used to evaluate nuclear staining of STAT3 (n-STAT3), which reflects the activated form of STAT3. The relationship between the n-STAT3 score and recurrence-free survival (RFS) was examined. RESULTS: The median n-STAT3 score was 105. RFS was compared between the two groups using the Kaplan-Meier method at a cutoff of 70 points (AUC = 0.60), calculated from the ROC curve based on recurrence. Ten-year and 20-year RFS were 87.5 and 83.1% in the high n-STAT3 group (n = 764) and 77.7 and 72.6% in the low n-STAT3 group (n = 371), respectively. The high n-STAT3 group had a significantly better RFS (P < 0.0001). Age (≥55 years), tumor size (≥4 cm), extrathyroidal extension, larger maximum lymph node size (≥30 mm), and low n-STAT3 levels were associated with poor RFS on univariate and multivariate analyses. CONCLUSION: n-STAT3 scores in cases with PTC were associated with favorable prognosis. Further studies are required to elucidate the mechanism.