title: Cellular proliferative fraction measured with topoisomerase IIalpha predicts malignancy in endocrine pancreatic tumors.
abstract: BACKGROUND
  Endocrine pancreatic tumors (EPTs) are rare lesions with varying biological behavior. Establishing malignancy is a challenge for clinicians and pathologists.
  
  
  OBJECTIVE
  To establish the role of proliferative, apoptotic, angiogenic, and hormonal markers as predictors of malignancy in EPTs.
  
  
  METHODS
  Paraffin-embedded EPT samples were studied for prognostic markers.
  
  
  METHODS
  Twenty-one consecutive patients with a diagnosis of EPT.
  
  
  METHODS
  The proliferative fraction (topoisomerase IIalpha), microvascular density (CD34), vascular endothelial growth factor expression, and estrogen receptor-beta (ERbeta) expression were studied by immunohistochemistry on all EPTs. Apoptosis was also assessed with terminal deoxynucleotidyl transferase nick-end labeling.
  
  
  RESULTS
  We identified 13 benign and 8 malignant tumors. Topoisomerase IIalpha was significantly increased in malignant tumors (P =.001), while there were no differences in apoptosis, microvascular density, or vascular endothelial growth factor expression in association with malignancy. No correlation could be identified between microvascular density and vascular endothelial growth factor expression, and ERbeta was not detected. A receiver operating characteristic curve for topoisomerase IIalpha disclosed that above a labeling index of 13, the test had 88% sensitivity and 100% specificity for predicting malignancy.
  
  
  CONCLUSIONS
  Cellular proliferation measured with topoisomerase IIalpha is a simple prognostic marker for malignancy in EPTs, unlike apoptosis, angiogenesis, or the presence of ERbeta, which were not associated with malignant behavior. These findings designate a defined field for future research on endocrine pancreatic carcinogenesis and a possible target for chemotherapeutic agents.
authors.affiliation: Department of Gastroenterology, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Mexico City, Mexico.
authors.forename: Jose Luis
authors.initials: JL
authors.lastname: Diaz-Rubio
authors.forename: Andres
authors.initials: A
authors.lastname: Duarte-Rojo
authors.forename: Milena
authors.initials: M
authors.lastname: Saqui-Salces
authors.forename: Armando
authors.initials: A
authors.lastname: Gamboa-Dominguez
authors.forename: Guillermo
authors.initials: G
authors.lastname: Robles-Diaz
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000951:Antigens, Neoplasm; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000032:analysis*; D002455:Cell Division; D004250:DNA Topoisomerases, Type II / Q000032:analysis*; D004268:DNA-Binding Proteins; D047629:Estrogen Receptor beta; D005260:Female; D015408:Gastrinoma / Q000098:blood supply / Q000201:enzymology / Q000473:pathology*; D006801:Humans; D020287:In Situ Nick-End Labeling; D007340:Insulinoma / Q000098:blood supply / Q000201:enzymology / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000032:analysis*; D009389:Neovascularization, Pathologic / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000201:enzymology / Q000473:pathology*; D011379:Prognosis; D012372:ROC Curve; D011960:Receptors, Estrogen / Q000032:analysis; D012680:Sensitivity and Specificity; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D047629:Estrogen Receptor beta; D009363:Neoplasm Proteins; D011960:Receptors, Estrogen; D042461:Vascular Endothelial Growth Factor A; D004250:DNA Topoisomerases, Type II