Disruptions of the p16-CDK4/cyclin D1-pRb pathway (RB pathway) and the p14A
RF-MDM2-p53 pathway (p53 pathway) are important mechanisms in the developme
nt of human malignancies. In this study, we investigated RB and p53 pathway
s in 46 epithelial ovarian cancers (EOCs). In the RB pathway, 16 (34.8%) of
46 cases had p16 gene alterations or loss of expression. The deletion of t
he p16 gene was a rare event. In 7 cases, we observed methylation in the 5
' CpG island in the promoter region of the p16 gene. Abnormal expressions o
f pRb and CDK4/cyclin DI were 10.9% and 30.4%, respectively. In the p53 pat
hway, 10 (21.7%) of 46 cases had p14ARF gene alterations or abnormal expres
sion. In 4 cases, methylation in the 5 ' CpG island in the promoter region
of the p14ARF gene was present. MDM2 overexpression was a rare event Thirty
-six (78.3%) of 46 patients had p53 gene alterations or expression. In our
studied cases, p14ARF abnormalities were independent of p16 abnormalities.
Abnormal RB and p53 pathways were present in 60.9% and 80.4% of cases, resp
ectively. In conclusion, disruptions of p53 and RB pathways are frequent ev
ents and the inverse correlations were present between the abnormality of p
16 and p14ARF in EOCs. Copyright (C) 2001 by W.B. Saunders Company.