High cyclin E staining index in blastemal, stromal or epithelial cells is correlated with tumor aggressiveness in patients with nephroblastoma.
OBJECTIVE
Identifying among nephroblastoma those with a high propensity for distant metastases using cell cycle markers: cyclin E as a regulator of progression through the cell cycle and Ki-67 as a tumor proliferation marker, since both are often deregulated in many human malignancies.


RESULTS
A staining index (SI) was obtained by immunohistochemistry using anti-cyclin E and anti-Ki-67 antibodies in paraffin sections of 54 postchemotherapy nephroblastoma including 42 nephroblastoma without metastasis and 12 with metastases. Median cyclin E and Ki-67 SI were 46% and 33% in blastemal cells, 30% and 10% in stromal cells, 37% and 29.5% in epithelial cells. The highest values were found for anaplastic nephroblastoma. A correlation between cyclin E and Ki-67 SI was found for the blastemal component and for the epithelial component. Univariate analysis showed prognostic significance for metastases with cyclin E SI in stromal cells, epithelial cells and blastemal cells (p = 0.03, p = 0.01 and p = 0.002, respectively) as well as with Ki-67 SI in blastema (p<10(-4)). The most striking data were that both cyclin E SI and blastemal Ki-67 SI discriminated between patients with metastases and patients without metastasis among intermediate-risk nephroblastoma.


CONCLUSIONS
Our findings show that a high cyclin E SI in all components of nephroblastoma is correlated with tumor aggressiveness and metastases, and that assessment of its expression may have prognostic value in the categorization of nephroblastoma.
Berrebi
Dominique
D
Assistance Publique-Hôpitaux de Paris, Hôpital Robert Debré, Service d'Anatomie et de Cytologie Pathologiques, Paris, France. dominique.berrebi@rdb.ap-hop-paris.fr
Leclerc
Julie
J
Schleiermacher
Gudrun
G
Zaccaria
Isabelle
I
Boccon-Gibod
Liliane
L
Fabre
Monique
M
Jaubert
Francis
F
El Ghoneimi
Alaa
A
Jeanpierre
Cécile
C
Peuchmaur
Michel
M
D019927:Cyclin E / Q000378:metabolism*; D004847:Epithelial Cells / Q000378:metabolism*; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism; D017154:Stromal Cells / Q000378:metabolism*; D009396:Wilms Tumor / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology
D019927:Cyclin E; D019394:Ki-67 Antigen