OBJECTIVE: To examine the cyclin D1 mRNA expression level in ovarian tumor
samples as compared with normal ovaries and to determine the relationship b
etween cyclin D1 overexpression and p53 mutation status in ovarian tumors.
METHODS: mRNA was isolated and cDNA was prepared from 27 epithelial ovarian
tumors (3 tumors of low malignant potential (LMP) and 24 cancers) and 6 no
rmal ovaries. The cyclin D1 sequences were amplified by using a thermal cyc
ler in parallel with the beta-tubulin gene as an internal control. The cycl
in D1 mRNA expression level relative to beta-tubulin was determined by P-32
phosphoimager analysis. To confirm the overexpression of the cyclin D1 pro
tein in ovarian tumor cells, immunostaining was performed. The p53 gene mut
ation status was examined by direct cDNA sequencing.
RESULTS: mRNA levels of cyclin D1 were significantly higher in 21 (78%) of
the 27 ovarian tumors than in normal ovaries. Cyclin D1 overexpression was
detected in ovarian LMP tumors as well as in ovarian cancer cases. Positive
immunostaining of cyclin D1 protein was observed in 10 of 18 (56%) ovarian
tumors examined. p53 mutations were found in 11 (61%) of 18 ovarian tumors
. Of 11 ovarian tumor cases with p53 mutations, 5 showed overexpression of
cyclin D1. All 7 ovarian tumor cases without p53 mutations showed significa
nt cyclin D1 mRNA overexpression.
CONCLUSION: Cyclin D1 overexpression seems to be an early genetic event in
ovarian tumor development. Although p53 may be one of the proteins whose fu
nction regulates the expression of G1 cyclins, ovarian tumors with no p53 m
utation consistently showed cyclin D1 overexpression. Cyclin D1 overexpress
ion may play an important role in the tumorigenesis of epithelial ovarian t
umors. Copyright (C) 1999 by the Society for Gynecologic Investigation.