High cyclin E staining index in blastemal, stromal or epithelial cells is correlated with tumor aggressiveness in patients with nephroblastoma

Abstract

Purpose: Identifying among nephroblastoma those with a high propensity for distant metastases using cell cycle markers: cyclin E as regulator of progression through the cell cycle and KI-67 as a tumor proliferation marker, since both are often deregulated in many human malignancies. Methodology/Principal Findings: A staining index (SI) was obtained by immunohistochemistry using anti-cyclin E and anti-Ki-67 antibodies in paraffin sections of 54 postchemotheraphy 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. © 2008 Berrebi et al.