The clinicopathological and prognostic significances of nuclear factor-kappa B (NF-κB) activation in papillary thyroid carcinoma : 갑상선 유두암에서 Nuclear factor-kappa B (NF-κB)의 임상-병리학적 중요성 및 예후에 미치는 영향

다국어 초록 (Multilingual Abstract)

Purpose: Nuclear factor-κB (NF-κB) is involved in proliferation, angiogenesis, and metastasis in various malignancies; however, little is known about the role of NF-κB and the associated pathway in papillary thyroid carcinoma (PTC). The purpose of this study is to elucidate the clinicopathological and prognostic significances of the NF-κB signaling pathway in PTC.
Materials and Methods: One-hundred twenty two patients with conventional PTC were investigated NF-κB RelA nuclear expression by immunohistochemistry and the correlation between NF-κB RelA nuclear expression and clinicopathological parameters including proliferation index, BRAFV600E mutation, cullin-1 expression and the presence of psammoma body (PB).
Results: Among 122 conventional PTCs, NF-κB RelA nuclear expression was found in 91 PTCs (74.6%). There were significant differences in extrathyroidal extension (P = 0.031), nodal metastasis (P = 0.021) and BRAFV600E mutation (P = 0.039), between NF-κB-positive and negative PTCs. NF-κB RelA nuclear expression was showed more frequent in overt PTCs (larger than 1 cm) than papillary thyroid microcarcinomas (PMCs) (P = 0.001). The expressions of cullin-1, which is involved in ubiquitination of phosphorylated IκBα, were found in 84 of 108 PTCs (77.8%). The nuclear expressions of NF-κB RelA were highly showed in cullin-1-positive PTCs than in cullin-1-negative PTCs (83.3% vs. 54.2%, respectively) (P = 0.003). The proliferation index was strongly associated with NF-κB nuclear expression (P = 0.045) and cullin-1 expression (P = 0.009), but not with BRAFV600E mutation (P = 0.141). The presence of PBs was found in 83 of 122 PTCs (68.0%) and significantly correlated with tumor size group and lymph node metastasis (P = 0.018 and P < 0.001, respectively), but not with any other clinicopathological parameters. Extratumoral PBs were only identified in 39 of 83 PTCs with PBs (47.0%) and significantly correlated with higher incidences of tumor multifocality, extrathyroidal extension, and nodal metastasis compared to PTCs with no extratumoral PBs (P < 0.001, P = 0.045 and P < 0.001, respectively). There was significant correlation between NF-κB nuclear expression and the presence of PBs (P = 0.023). Indeed, the presence of intratumoral PBs was significantly associated with NF-κB nuclear expression (P = 0.008).
Conclusion: Taken together, these results suggest that NF-κB RelA activation may contribute to tumor growth and aggressiveness and PB formation of PTC after tumor transformation. The expression pattern of NF-κB may serve as a prognostic marker and a potential therapeutic target.

목차 (Table of Contents)

• ABSTRACT = ⅰ
• TABLE OF CONTENTS = ⅳ
• LIST OF TABLES = ⅴ
• LIST OF FIGURES = ⅶ
• LIST OF ABBREVIATIONS AND SYMBOLS = ⅷ
• Ⅰ. INTRODUCTION = 1
• Ⅱ. MATERIALS AND METHODS = 6
• Ⅲ. RESULTS = 12
• Ⅳ. DISCUSSION = 33
• Ⅴ. CONCLUSION = 42
• REFERENCES = 43
• 국문요지 = 52
• APPENDIX = 54
• ACKNOWDGEMENTS = 62