Prognostic Value of Nuclear DNA Quantification and Cyclin A in Epithelial Ovarian Cancer

Lee, Chong Seung; Cho, Nam Hoon; Kim, Young Tae; Kim, Sung Hoon; Roh, Jong Hwan; Kim, Jae Wook

Abstract

OBJECTIVE
This study was carried out to investigate the relationship between DNA ploidy, S-phase fraction (SPF), expression of cyclin A and clinical prognostic factors including stage, grade, CA-125 and residual tumor size in epithelial ovarian cancer, and to evaluate the association between DNA ploidy, SPF, expression of cyclin A and 3-year survival.
METHODS
Study group consisted of 31 cases of epithelial ovarian cancer, 10 of borderline ovarian tumor and 5 of benign ovarian tumor diagnosed at the department of Obstet. and Gynecol. in Yonsei University College of Medicine, Seoul, Korea from Feb. 2000 to Jan. 2003. All patients underwent staging-laparotomy and postoperative chemotherapy. The level of CA-125 was assessed after 6th postoperative chemotherapy with cut-off value of 35 U/mL. DNA ploidy and SPF were evaluated by flow-cytometry of fresh ovarian tissue obtained at the operative field. The expression of cyclin A was evaluated by immuno-histochemical stain. Expression of 5% was considered as positive. Statistical analysis was done by two-sample t-test, chi-square test, and Kaplan-Meier survival curve using SPSS ver 11.0 software.
RESULTS
In 46 ovarian tumors aneuploidy, SPF and expression of cyclin A were significantly higher in epithelial ovarian cancer as compared with benign and borderline tumors (p=0.004, 0.001, 0.001, respectively). Number of aneuploidy, SPF and expression of cyclin A were significantly higher in patients with higher grade, more advanced stage, higher level of CA-125 (more than 35 U/mL) and more than 2 cm of residual tumor size (p=0.004, 0.009, 0.05, 0.002 in aneuploidy; p=0.06, 0.01, 0.04, 0.007 in SPF; p=0.03, 0.004, 0.06, 0.02 in cyclin A). Aneuploidy and expressions of more than 10% of SPF and cyclin A were also associated with poorer overall survival (p=0.02, 0.02, <0.0001, respectively). Significantly positive correlations were observed among these factors.
CONCLUSION
Number of aneuploidy, percentage of SPF and expression of cyclin A were higher in more advanced stage, higher grade, higher CA-125 and more than 2 cm of residual tumor size and associated with poorer overall survival. Thus DNA flow-cytometry and estimation of expression of cyclin A may provide major information about prognosis of disease in epithelial ovarian cancer patients.