title: Negative Expression of CPSF2 Predicts a Poorer Clinical Outcome in Patients with Papillary Thyroid Carcinoma.
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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: 1 Department of Surgery, University of Ulsan College of Medicine , Seoul, Korea.
authors.forename: Tae Yon
authors.initials: TY
authors.lastname: Sung
authors.affiliation: 2 Department of Internal Medicine, University of Ulsan College of Medicine , Seoul, Korea.
authors.forename: Mijin
authors.initials: M
authors.lastname: Kim
authors.affiliation: 2 Department of Internal Medicine, University of Ulsan College of Medicine , Seoul, Korea.
authors.forename: Tae Yong
authors.initials: TY
authors.lastname: Kim
authors.affiliation: 2 Department of Internal Medicine, University of Ulsan College of Medicine , Seoul, Korea.
authors.forename: Won Gu
authors.initials: WG
authors.lastname: Kim
authors.affiliation: 3 Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine , Seoul, Korea.
authors.forename: Yangsoon
authors.initials: Y
authors.lastname: Park
authors.affiliation: 3 Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine , Seoul, Korea.
authors.forename: Dong Eun
authors.initials: DE
authors.lastname: Song
authors.affiliation: 2 Department of Internal Medicine, University of Ulsan College of Medicine , Seoul, Korea.
authors.forename: Su-Yeon
authors.initials: SY
authors.lastname: Park
authors.affiliation: 2 Department of Internal Medicine, University of Ulsan College of Medicine , Seoul, Korea.
authors.forename: Hyemi
authors.initials: H
authors.lastname: Kwon
authors.affiliation: 2 Department of Internal Medicine, University of Ulsan College of Medicine , Seoul, Korea.
authors.forename: Yun Mi
authors.initials: YM
authors.lastname: Choi
authors.affiliation: 2 Department of Internal Medicine, University of Ulsan College of Medicine , Seoul, Korea.
authors.forename: Eun Kyung
authors.initials: EK
authors.lastname: Jang
authors.affiliation: 2 Department of Internal Medicine, University of Ulsan College of Medicine , Seoul, Korea.
authors.forename: Min Ji
authors.initials: MJ
authors.lastname: Jeon
authors.affiliation: 2 Department of Internal Medicine, University of Ulsan College of Medicine , Seoul, Korea.
authors.forename: Young Kee
authors.initials: YK
authors.lastname: Shong
authors.affiliation: 1 Department of Surgery, University of Ulsan College of Medicine , Seoul, Korea.
authors.forename: Suck Joon
authors.initials: SJ
authors.lastname: Hong
authors.affiliation: 2 Department of Internal Medicine, University of Ulsan College of Medicine , Seoul, Korea.
authors.forename: Won Bae
authors.initials: WB
authors.lastname: Kim
mesh_terms: D000328:Adult; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D002277:Carcinoma / Q000378:metabolism* / Q000628:therapy; D002291:Carcinoma, Papillary; D039223:Cleavage And Polyadenylation Specificity Factor / Q000235:genetics / Q000378:metabolism*; D004252:DNA Mutational Analysis; D018572:Disease-Free Survival; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009154:Mutation; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local; D014411:Neoplastic Stem Cells; D016017:Odds Ratio; D015995:Prevalence; D011379:Prognosis; D016016:Proportional Hazards Models; D056910:Republic of Korea; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000378:metabolism* / Q000628:therapy; D013965:Thyroidectomy; D046888:Tissue Array Analysis; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; C000609186:CPSF2 protein, human; D039223:Cleavage And Polyadenylation Specificity Factor