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Cyclin E mRNA Overexpression in Epithelial Ovarian Cancers: Inverse Correlation with p53 Protein Accumulation

Department of Obstetrics and Gynecology, Kure National Hospital, Chugoku Cancer Center, Kure; Department of Obstetrics and Gynecology, Hiroshima University School of Medicine, Hiroshima, Japan; Departments of Obstetrics and Gynecology and Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences, Little Rock, Arkansas

Kazushi Shigemasa, MD

Department of Obstetrics and Gynecology, Kure National Hospital, Chugoku Cancer Center, Kure; Departments of Obstetrics and Gynecology and Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences, Little Rock, Arkansas; Department of Obstetrics and Gynecology, Hiroshima University School of Medicine, 1-2-3, Kasumi, Minami-ku, Hiroshima 734-8551, Japan kaz{at}mcai.med.hiroshima-u.ac.jp

Yuko Shiroyama, MD

Tomoyo Kusuda, MD

Tsuneo Fujii, MD

Tim H. Parmley, MD

Timothy J. O'Brien, PhD

Koso Ohama, MD

Department of Obstetrics and Gynecology, Kure National Hospital, Chugoku Cancer Center, Kure; Department of Obstetrics and Gynecology, Hiroshima University School of Medicine, Hiroshima, Japan; Departments of Obstetrics and Gynecology and Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences, Little Rock, Arkansas

Objective: We investigated the relationship between cyclin E mRNA overexpression and p53 protein accumulation in epithelial ovarian cancers.

Methods: mRNA was isolated and cDNA was prepared from 36 epithelial ovarian tumors (three adenomas, three low malignant potential tumors, and 30 carcinomas), and six normal ovaries. The cyclin E mRNA expression levels relative to an internal control, ß-tubulin, were determined by semiquantitative polymerase chain reaction (PCR). Cyclin E and p53 protein expression in ovarian cancer tissues were examined by immunohistochemistry using the same series of samples. Fisher exact test of significance and an unpaired t test were used for statistical analysis.

Results: Considerable levels of cyclin E mRNA were detected in all normal ovaries and ovarian tumor samples examined by semiquantitative PCR amplification. mRNA levels of cyclin E were significantly higher in nine of 30 (30%) ovarian cancers compared with those in normal ovaries. The immunohistochemical expression of cyclin E protein was confirmed in the nuclei of tumor cells in 13 of 30 (43%) ovarian cancers. p53 protein accumulation was detected in 12 of 30 (40%) ovarian cancers examined. There was a significant inverse correlation between cyclin E mRNA overexpression and p53 protein accumulation (P <.01, Fisher exact test).

Conclusions: Cyclin E mRNA overexpression frequently occurs in ovarian cancers without p53 protein accumulation. Cyclin E might have an important effect on the development of a limited number of ovarian cancers.

Key Words: Cyclin E • p53 • overexpression • ovarian cancer

Journal of the Society for Gynecologic Investigation, Vol. 8, No. 3, 179-185 (2001)
DOI: 10.1177/107155760100800310


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