Survivin: a novel neuroendocrine marker for pheochromocytoma.
OBJECTIVE
To study survivin expression in human adrenal medulla and in benign and malignant pheochromocytoma tissue as a tool to predict tumor metastatic potential and prognosis.


METHODS
Blinded study to assess the role of the anti-survivin antibody in chromaffin cells.


METHODS
We performed immunohistochemistry with a purified rabbit-polyclonal anti-survivin antibody on 39 formalin-fixed and paraffin-embedded pheochromocytoma/paraganglioma specimens, and on 10 normal adrenal medulla samples from patients unaffected by a chromaffin cell tumor. Fourteen samples were from 14 patients with benign pheochromocytoma (<8 year follow-up, mean 5.2 years), 18 specimens were from 12 patients with malignant pheochromocytoma (<13 year follow-up, mean 6.3 years), 5 samples were from 2 patients with malignant paraganglioma (<6 year follow-up, mean 4 years), and 2 specimens from 2 patients with benign paraganglioma (<7 year follow-up, mean 5.5 years). Malignancy was defined by metastases in non-chromaffin tissues. Staining intensity with the anti-survivin antibody was scored from 0 (none) to 3+ (heavy). Tissues from human kidney, breast, and melanoma served as controls.


RESULTS
All pheochromocytoma/paraganglioma specimens stained either 2+ or 3+. By analysis of variance (ANOVA), there was no statistically significant difference between the staining intensity of benign and malignant samples. All normal adrenal medulla specimens stained positively with anti-survivin but to a lesser degree than the chromaffin cell tumors (P<0.01).


CONCLUSIONS
Based on these findings, we conclude that (i) survivin may represent a novel neuroendocrine marker for chromaffin cell tumors, and (ii) survivin does not appear to reliably distinguish benign from malignant pheochromocytomas/paragangliomas and thus does not identify patients at risk of recurrent disease.
Koch
Christian A
CA
National Institutes of Health (NIH), National Institute of Child Health and Human Development, Bethesda, Maryland 20892, USA. Kochc@exchange.nih.gov
Vortmeyer
Alexander O
AO
Diallo
Raihanatou
R
Poremba
Christopher
C
Giordano
Thomas J
TJ
Sanders
Donita
D
Bornstein
Stefan R
SR
Chrousos
George P
GP
Pacak
Karel
K
D000293:Adolescent; D000310:Adrenal Gland Neoplasms / Q000378:metabolism* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers; D019439:Chromaffin Cells / Q000378:metabolism; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007202:Indicators and Reagents; D051034:Inhibitor of Apoptosis Proteins; D008297:Male; D008869:Microtubule-Associated Proteins; D008875:Middle Aged; D009363:Neoplasm Proteins; D010673:Pheochromocytoma / Q000378:metabolism* / Q000473:pathology; D000077022:Survivin; D016707:Tissue Fixation
C107489:BIRC5 protein, human; D015415:Biomarkers; D002868:Chromosomal Proteins, Non-Histone; D007202:Indicators and Reagents; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D000077022:Survivin