Negative Expression of CPSF2 Predicts a Poorer Clinical Outcome in Patients with Papillary Thyroid Carcinoma

Thyroid. 2015 Sep;25(9):1020-5. doi: 10.1089/thy.2015.0079. Epub 2015 Aug 3.

Abstract

Background: The BRAF(V600E) mutation is a promising prognostic biomarker for patients with papillary thyroid carcinoma (PTC), but its prevalence differs widely among different geographic regions. A recent study reported that loss of the Cleavage and Polyadenylation Specificity Factor Subunit 2 (CPSF2) gene was associated with increased cellular invasion, cancer stem cells, and aggressiveness of PTC. This study aimed at evaluating CPSF2 protein expression as a prognostic marker for PTC in a region with a high prevalence of the BRAF(V600E) mutation, Korea.

Methods: This study included 159 patients with classical PTC who underwent a total thyroidectomy and received ablative doses of (131)I. The expression of CPSF2 protein was evaluated by immunohistochemistry and graded semi-quantitatively. The presence of the BRAF(V600E) mutation was evaluated by direct sequencing.

Results: Negative protein expression of CPSF2 was observed in 34 (21.3%) of the 159 PTCs. In multivariate analysis, negative CPSF2 expression was significantly associated with cervical lymph node metastasis (odds ratio [OR]=2.56, p=0.28), and distant metastasis (OR=3.48, p=0.02). After adjusting for age, sex, tumor size, extrathyroidal invasion, lymphovascular invasion, and the BRAF(V600E) mutation, the CPSF2-negative group had a significantly lower recurrence-free survival compared to the CPSF2-positive group (hazard ratio=2.14, p=0.03).

Conclusion: Negative protein expression of CPSF2 is independently associated with a poor clinical outcome in PTC. CPSF2 could be a useful prognostic marker for PTC in regions with a high prevalence of the BRAF(V600E) mutation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Carcinoma / metabolism*
  • Carcinoma / therapy
  • Carcinoma, Papillary
  • Cleavage And Polyadenylation Specificity Factor / genetics
  • Cleavage And Polyadenylation Specificity Factor / metabolism*
  • DNA Mutational Analysis
  • Disease-Free Survival
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Mutation
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • Neoplasm Recurrence, Local
  • Neoplastic Stem Cells
  • Odds Ratio
  • Prevalence
  • Prognosis
  • Proportional Hazards Models
  • Republic of Korea
  • Thyroid Cancer, Papillary
  • Thyroid Neoplasms / metabolism*
  • Thyroid Neoplasms / therapy
  • Thyroidectomy
  • Tissue Array Analysis
  • Treatment Outcome

Substances

  • Biomarkers, Tumor
  • CPSF2 protein, human
  • Cleavage And Polyadenylation Specificity Factor