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 (> 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).


CONCLUSIONS
This study shows that cyclin E overproduction is of adverse prognostic significance in adrenocortical tumors.
Tissier
Frédérique
F
Service d'Anatomie Pathologique, Hopital Cochin, AP-HP, 75014 Paris, France. frederique.tissier@cch-ap-hop-paris.fr
Louvel
Albert
A
Grabar
Sophie
S
Hagnéré
Anne-Marie
AM
Bertherat
Jérôme
J
Vacher-Lavenu
Marie-Cécile
MC
Dousset
Bertrand
B
Chapuis
Yves
Y
Bertagna
Xavier
X
Gicquel
Christine
C
D000306:Adrenal Cortex Neoplasms / Q000737:chemistry* / Q000235:genetics / Q000473:pathology; D000328:Adult; D002880:Chromosomes, Human, Pair 11; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics; D019927:Cyclin E / Q000032:analysis*; D018572:Disease-Free Survival; D005260:Female; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D007335:Insulin-Like Growth Factor II / Q000235:genetics; D019656:Loss of Heterozygosity; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D024182:Uniparental Disomy
D019927:Cyclin E; D007335:Insulin-Like Growth Factor II