Associations of the BRAF V600E Mutation and PAQR3 Protein Expression with Papillary Thyroid Carcinoma Clinicopathological Features

Pathol Oncol Res. 2020 Jul;26(3):1833-1841. doi: 10.1007/s12253-019-00779-x. Epub 2019 Nov 22.

Abstract

The BRAFV600E mutation is the most prevalent genetic event in patients with papillary thyroid cancer (PTC). However, no study has investigated the expression of PAQR3 in papillary thyroid tissues in relation to the BRAFV600E mutation and the clinicopathological features of PTC patients. Furthermore, the potential associations of the BRAFV600E mutation, PAQR3 expression and clinicopathological parameters in the cancerous tissues of PTC patients have not been investigated. This study was conducted on 60 patients with PTC who were treated surgically at our institution from 2017 to 2018. PCR was used to amplify DNA by the amplification refractory mutation system (ARMS) method to detect BRAFV600E gene mutations. In addition, immunohistochemical techniques were utilized to assess PAQR3 expression in tumor tissue sections. The BRAFV600E mutation was associated with lymph node metastasis (LNM, p < 0.05) but not with other clinicopathological features. Low PAQR3 expression was associated with extrathyroidal extension and LNM (χ2 = 7.143, p = 0.009; χ2 = 6.459, p = 0.014, respectively). Furthermore, a statistically significant association was observed between chronic lymphocytic thyroiditis and LNM (χ2 = 5.275, p = 0.0250). A linear relationship between the BRAFV600E mutation and PAQR3 protein expression has not been identified. These factors may be independent risk factors of extrathyroidal extension and LNM in PTC and be used to indicate the invasiveness of PTC tumors. Higher quality, multivariate analyses based on larger samples from around the world are urgently needed to further validate and revise our findings in the future.

Keywords: BRAF gene; Extrathyroidal extension; Lymph node metastasis (LNM); PAQR3; Papillary thyroid microcarcinoma; Thyroid cancer.

MeSH terms

  • Adult
  • Asian People / genetics
  • Biomarkers, Tumor / analysis*
  • Female
  • Humans
  • Intracellular Signaling Peptides and Proteins / biosynthesis*
  • Male
  • Membrane Proteins / biosynthesis*
  • Middle Aged
  • Mutation*
  • Proto-Oncogene Proteins B-raf / genetics*
  • Thyroid Cancer, Papillary / genetics
  • Thyroid Cancer, Papillary / metabolism
  • Thyroid Cancer, Papillary / pathology*
  • Thyroid Neoplasms / genetics
  • Thyroid Neoplasms / metabolism
  • Thyroid Neoplasms / pathology*

Substances

  • Biomarkers, Tumor
  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins
  • PAQR3 protein, human
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf