title: Prognostic significance of human pituitary tumor-transforming gene immunohistochemical expression in differentiated thyroid cancer.
abstract: BACKGROUND
  Human securin pituitary tumor-transforming gene (hPTTG) is overexpressed in a variety of primary neoplasias, including differentiated thyroid cancer (DTC).
  
  
  OBJECTIVE
  The objective of this study was to examine the immunohistochemical expression of hPTTG in DTC and its association with known prognostic factors.
  
  
  METHODS
  hPTTG expression was analyzed by immunostaining on paraffin-embedded tissues. Clinical data were used to determine any associations between the expression of hPTTG and prognostic variables of DTC. A median follow-up of 43 months allowed us to analyze the persistence of disease and the response to radioiodine therapy.
  
  
  METHODS
  The study was conducted at a tertiary university hospital.
  
  
  METHODS
  Ninety-five patients undergoing surgical resection for DTC (n = 60) or benign nodular thyroid disease (n = 35) were studied.
  
  
  METHODS
  The main outcome measure was the association between hPTTG expression and prognostic factors in DTC.
  
  
  RESULTS
  Among DTC cases, 21 (35%) had low and 39 (65%) had high hPTTG immunostaining. Adjacent nonneoplastic thyroid tissue was largely unstained. Among benign nodular thyroid disease cases, immunostaining was detected focally in eight (22.8%). A significant association was found between hPTTG expression and the presence of nodal (P < 0.01) or distant metastases (P < 0.05). A significant association with TNM was also found, because 83.3% of advanced TNM stages showed elevated hPTTG (P < 0.05). The association between hPTTG overexpression and decreased radioiodine uptake during follow-up was also significant (P < 0.05). The expression levels of hPTTG were confirmed as an independent prognostic factor for persistent disease (relative risk, 3.0; 95% confidence interval, 1.1-8.7; P < 0.05).
  
  
  CONCLUSIONS
  Immunohistochemical analysis of hPTTG is of potential value in the determination of tumor aggressiveness in DTC.
authors.affiliation: Department of Pathology, Hospital Universitario Virgen del Rocío, Avenida Manuel Siurot s/n, Seville 41013, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: Sáez
authors.forename: M Asunción
authors.initials: MA
authors.lastname: Martínez-Brocca
authors.forename: Carolina
authors.initials: C
authors.lastname: Castilla
authors.forename: Alfonso
authors.initials: A
authors.lastname: Soto
authors.forename: Elena
authors.initials: E
authors.lastname: Navarro
authors.forename: María
authors.initials: M
authors.lastname: Tortolero
authors.forename: José A
authors.initials: JA
authors.lastname: Pintor-Toro
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Japón
mesh_terms: D000236:Adenoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000368:Aged; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D006044:Goiter, Nodular / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D007454:Iodides / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D016612:Paraffin Embedding; D011379:Prognosis; D016016:Proportional Hazards Models; D064249:Securin; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*
chemical_list: D007454:Iodides; D009363:Neoplasm Proteins; D064249:Securin; C578002:pituitary tumor-transforming protein 1, human