Stomatin-like protein 2 overexpression in papillary thyroid carcinoma is significantly associated with high-risk clinicopathological parameters and BRAFV600E mutation

APMIS. 2016 Apr;124(4):271-7. doi: 10.1111/apm.12505. Epub 2016 Jan 11.

Abstract

Stomatin-like protein 2 (SLP-2), a member of the stomatin protein family, has emerged as a potential molecular hallmark of tumor progression in several human malignancies. The aim of this study was to analyze SLP-2 expression pattern in benign and malignant thyroid tumors (n = 210) and to examine its relationship with clinicopathological parameters and BRAFV600E mutation in thyroid cancer. SLP-2 immunohistochemical expression was not detected in benign adenomas and was absent/weak in follicular and anaplastic carcinomas. High expression levels of SLP-2, found only in papillary thyroid carcinoma (PTC), particularly in the classical variant, were significantly associated with adverse clinicopathological parameters: lymph node metastasis (p = 0.002), extrathyroid invasion (p < 0.001), pT status (p < 0.001), and advanced tumor stage (p = 0.001). Additional genotyping of PTC cases for the BRAFV600E mutation revealed for the first time a close relation between SLP-2 overexpression and the presence of BRAF mutation (p = 0.02) with high positive rates of lymph node metastasis (70%) and extrathyroid invasion (80%) in these cases. The significant association of SLP-2 overexpression with unfavorable clinicopathological characteristics and BRAFV600E mutation indicates that SLP-2 may have a role in aggressiveness of BRAF-mutated PTC and that SLP-2 evaluation could be clinically useful in identification of high-risk PTC patients.

Keywords: BRAFV600E mutation; Stomatin-like protein 2; papillary thyroid carcinoma; thyroid; tumor progression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma, Follicular / diagnosis
  • Adenocarcinoma, Follicular / genetics
  • Adenocarcinoma, Follicular / pathology
  • Adenoma / diagnosis
  • Adenoma / genetics
  • Adenoma / pathology
  • Adult
  • Aged
  • Blood Proteins / genetics*
  • Carcinoma / diagnosis*
  • Carcinoma / genetics
  • Carcinoma / pathology
  • Carcinoma, Papillary
  • Case-Control Studies
  • Diagnosis, Differential
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Genotype
  • Humans
  • Lymphatic Metastasis
  • Male
  • Membrane Proteins / genetics*
  • Middle Aged
  • Mutation*
  • Neoplasm Staging
  • Neoplasms / diagnosis*
  • Neoplasms / genetics
  • Neoplasms / pathology
  • Prognosis
  • Proto-Oncogene Proteins B-raf / genetics*
  • Risk
  • Thyroid Cancer, Papillary
  • Thyroid Carcinoma, Anaplastic / diagnosis
  • Thyroid Carcinoma, Anaplastic / genetics
  • Thyroid Carcinoma, Anaplastic / pathology
  • Thyroid Gland / metabolism
  • Thyroid Gland / pathology
  • Thyroid Neoplasms / diagnosis*
  • Thyroid Neoplasms / genetics
  • Thyroid Neoplasms / pathology

Substances

  • Blood Proteins
  • Membrane Proteins
  • STOML2 protein, human
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf