Cyclin E correlates with malignancy and adverse prognosis in adrenocortical tumors

Objective: In many cases, the prognosis of an adrenocortical tumor cannot be determined from pathologic findings alone. We investigated cyclin E levels as a potential marker. Methods: We studied 57 tumors by immunohistochemical staining with an anticyclin E antibody. We also evaluated clinical and pathologic factors (McFarlane staging and Weiss score) and previously validated genetic markers (17p13 loss of heterozygosity, 11p15 uniparental disomy, and overexpression of the IGF-II gene) for these tumors. Disease-free survival was estimated in 49 patients who underwent curative surgery. Results: Cyclin E overproduction (greater than or equal to 5%) was associated with the malignant phenotype and was strongly correlated with tumor size (P < 0.0001), Weiss score (P < 0.0001) and the presence of genetic abnormalities in tumors (P < 0.001) (nonparametric Wilcoxon test and Fisher's exact test). Within a median follow-up of 44.1 months, seven patients exhibited a recurrence and two patients died from other causes. Cyclin E overproduction was significantly associated with shorter disease-free survival in univariate analysis (P = 0.016: RR: 7.6), as were histologic grade (Weiss score greater than or equal to 4: P = 0.0006: RR: 18), 17p13 LOH (P = 0.014, RR: 14.9), 11p15 UPD (P = 0.003. RR: 11.8) and overexpression of the IGF-II gene (P = 0.015, RR: 13.8). Conclusion: This study shows that cyclin E overproduction is of adverse prognostic significance in adrenocortical tumors.