Cellular proliferative fraction measured with topoisomerase IIalpha predicts malignancy in endocrine pancreatic tumors.
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.
Diaz-Rubio
Jose Luis
JL
Department of Gastroenterology, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Mexico City, Mexico.
Duarte-Rojo
Andres
A
Saqui-Salces
Milena
M
Gamboa-Dominguez
Armando
A
Robles-Diaz
Guillermo
G
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
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