title: Activation of nuclear factor-κB contributes to growth and aggressiveness of papillary thyroid carcinoma.
abstract: Nuclear factor-κB (NF-κB) is involved in proliferation, angiogenesis, and metastasis in various malignancies; however, the role of NF-κB in papillary thyroid carcinoma (PTC) has not been fully elucidated. The purpose of this study was to elucidate the role and clinicopathological significance of the NF-κB signaling pathway in PTC. We investigated NF-κB RelA expression in 122 patients with conventional PTC by immunohistochemistry, and evaluated the correlation between RelA expression and clinicopathological parameters, including BRAF(V600E) mutation. Nuclear expression of NF-κB RelA, regardless of cytoplasmic expression, was identified in 91 of 122 PTCs (74.6%), and was more frequent in PTCs larger than 1cm (overt PTC) (P=0.001). There were significant differences in clinicopathological parameters, such as extrathyroidal extension (P=0.031), nodal metastasis (P=0.021) and BRAF(V600E) mutation (P=0.039), between NF-κB-positive and negative PTCs. Proliferation index was strongly associated with NF-κB activation (P=0.045) but not with BRAF(V600E) mutation (P=0.141). Taken together, our results suggest that NF-κB RelA activation contributes, at least in part, to tumor growth and aggressiveness of PTC after tumor transformation. The expression pattern of NF-κB may serve as a prognostic marker and a potential therapeutic target.
authors.affiliation: Department of Pathology, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, South Korea.
authors.forename: Jung-Soo
authors.initials: JS
authors.lastname: Pyo
authors.forename: Guhyun
authors.initials: G
authors.lastname: Kang
authors.forename: Dong Hoon
authors.initials: DH
authors.lastname: Kim
authors.forename: Seoung Wan
authors.initials: SW
authors.lastname: Chae
authors.forename: Chanheun
authors.initials: C
authors.lastname: Park
authors.forename: Kyungeun
authors.initials: K
authors.lastname: Kim
authors.forename: Sung-Im
authors.initials: SI
authors.lastname: Do
authors.forename: Hyun Joo
authors.initials: HJ
authors.lastname: Lee
authors.forename: Joo Heon
authors.initials: JH
authors.lastname: Kim
authors.forename: Jin Hee
authors.initials: JH
authors.lastname: Sohn
mesh_terms: D000328:Adult; D014408:Biomarkers, Tumor / Q000032:analysis*; D002277:Carcinoma / Q000737:chemistry* / Q000235:genetics / Q000473:pathology / Q000601:surgery; D002291:Carcinoma, Papillary; D049109:Cell Proliferation; D016009:Chi-Square Distribution; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008197:Lymph Node Excision; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D011379:Prognosis; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000737:chemistry* / Q000235:genetics / Q000473:pathology / Q000601:surgery; D013965:Thyroidectomy; D046888:Tissue Array Analysis; D051996:Transcription Factor RelA / Q000032:analysis*; D047368:Tumor Burden
chemical_list: D014408:Biomarkers, Tumor; C498143:RELA protein, human; D051996:Transcription Factor RelA; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf