PMID- 15043465 OWN - NLM STAT- MEDLINE DCOM- 20040719 LR - 20210527 IS - 1543-2165 (Electronic) IS - 0003-9985 (Linking) VI - 128 IP - 4 DP - 2004 Apr TI - Cellular proliferative fraction measured with topoisomerase IIalpha predicts malignancy in endocrine pancreatic tumors. PG - 426-9 AB - CONTEXT: 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. DESIGN: Paraffin-embedded EPT samples were studied for prognostic markers. PATIENTS: Twenty-one consecutive patients with a diagnosis of EPT. MAIN OUTCOME MEASURES: 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. CONCLUSION: 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. FAU - Diaz-Rubio, Jose Luis AU - Diaz-Rubio JL AD - Department of Gastroenterology, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Mexico City, Mexico. FAU - Duarte-Rojo, Andres AU - Duarte-Rojo A FAU - Saqui-Salces, Milena AU - Saqui-Salces M FAU - Gamboa-Dominguez, Armando AU - Gamboa-Dominguez A FAU - Robles-Diaz, Guillermo AU - Robles-Diaz G LA - eng PT - Comparative Study PT - Evaluation Study PT - Journal Article PL - United States TA - Arch Pathol Lab Med JT - Archives of pathology & laboratory medicine JID - 7607091 RN - 0 (Antigens, Neoplasm) RN - 0 (Biomarkers, Tumor) RN - 0 (DNA-Binding Proteins) RN - 0 (Estrogen Receptor beta) RN - 0 (Neoplasm Proteins) RN - 0 (Receptors, Estrogen) RN - 0 (Vascular Endothelial Growth Factor A) RN - EC 5.99.1.3 (DNA Topoisomerases, Type II) SB - IM MH - Adolescent MH - Adult MH - Aged MH - Antigens, Neoplasm MH - Apoptosis MH - Biomarkers, Tumor/*analysis MH - Cell Division MH - DNA Topoisomerases, Type II/*analysis MH - DNA-Binding Proteins MH - Estrogen Receptor beta MH - Female MH - Gastrinoma/blood supply/enzymology/*pathology MH - Humans MH - In Situ Nick-End Labeling MH - Insulinoma/blood supply/enzymology/*pathology MH - Male MH - Middle Aged MH - Neoplasm Invasiveness MH - Neoplasm Proteins/*analysis MH - Neovascularization, Pathologic/pathology MH - Pancreatic Neoplasms/enzymology/*pathology MH - Prognosis MH - ROC Curve MH - Receptors, Estrogen/analysis MH - Sensitivity and Specificity MH - Vascular Endothelial Growth Factor A/analysis EDAT- 2004/03/27 05:00 MHDA- 2004/07/20 05:00 CRDT- 2004/03/27 05:00 PHST- 2004/03/27 05:00 [pubmed] PHST- 2004/07/20 05:00 [medline] PHST- 2004/03/27 05:00 [entrez] AID - OA3222 [pii] AID - 10.5858/2004-128-426-CPFMWT [doi] PST - ppublish SO - Arch Pathol Lab Med. 2004 Apr;128(4):426-9. doi: 10.5858/2004-128-426-CPFMWT.