Activation of nuclear factor-κB contributes to growth and aggressiveness of papillary thyroid carcinoma

Pathol Res Pract. 2013 Apr;209(4):228-32. doi: 10.1016/j.prp.2013.02.004. Epub 2013 Mar 5.

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.

MeSH terms

  • Adult
  • Biomarkers, Tumor / analysis*
  • Carcinoma / chemistry*
  • Carcinoma / genetics
  • Carcinoma / pathology
  • Carcinoma / surgery
  • Carcinoma, Papillary
  • Cell Proliferation
  • Chi-Square Distribution
  • DNA Mutational Analysis
  • Female
  • Humans
  • Immunohistochemistry
  • Lymph Node Excision
  • Lymphatic Metastasis
  • Male
  • Middle Aged
  • Mutation
  • Neoplasm Invasiveness
  • Neoplasm Staging
  • Prognosis
  • Proto-Oncogene Proteins B-raf / genetics
  • Thyroid Cancer, Papillary
  • Thyroid Neoplasms / chemistry*
  • Thyroid Neoplasms / genetics
  • Thyroid Neoplasms / pathology
  • Thyroid Neoplasms / surgery
  • Thyroidectomy
  • Tissue Array Analysis
  • Transcription Factor RelA / analysis*
  • Tumor Burden

Substances

  • Biomarkers, Tumor
  • RELA protein, human
  • Transcription Factor RelA
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf