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Service d'Anatomie Pathologique, Hopital Cochin, AP-HP, 75014 Paris, France. frederique.tissier@cch-ap-hop-paris.fr
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 (> or =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 > or =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.
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