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

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.

Prognostic Significance of Flow Cytometric Nuclear DNA Quantification in Ovarian Tumors / 대한산부인과학회잡지

OBJECTIVE: The aim of this study was to investigate the relationship of DNA ploidy, SPF to other surgicopathologic factors including stage, grade and CA-125 in ovarian cancer and to evaluate the association between CA-125, DNA ploidy, SPF and 2-year survival in ovarian cancer. METHODS: The study was prospective, which included 56 patients with ovarian tumors who were treated at the Department of Obstetrics and Gynecology, Yonsei University College of Medicine from Feb. 2000 to Jan. 2003. There were 7 benign tumors, 9 borderline tumors and 40 malignant tumors. All patients underwent surgical operation for fresh tissue. All specimens for histopathologic grading and stage were classified according to WHO criteria and FIGO stage. DNA ploidy groups were divided into two groups, diploidy and aneuploidy. DNA ploidy and S-phase fraction (SPF) were analyzed by flow cytometry in fresh surgicalspecimens from primary ovarian tumor. CA-125 was measured at diagnosis and after 6th courses of chemotherapy. RESULTS: Of the Benign tumors, 85.7% were diploidy, 14.3% were aneuploidy. Of the borderline tumors, 88.9% were diploidy, 11.1% were aneuploidy, 60.0% of malignant tumors were diploidy, 40.0% were aneuploidy. In relation between grade and DNA quantification, grade was not significantly associated with DNA ploidy (p=0.07), SPF (p=0.08). In the relationship of stage to DNA quantification, aneuploidy was associated with advanced stage (p=0.2), mean value of SPF was significantly high in advanced stage (stage III+IV) (p=0.04). In the DNA ploidy and SPF, mean value of SPF was 5.5 +/- 4.6% in diploidy and 13.6 +/- 12.8% in aneuploidy. The difference was significant (p=0.03). The serum CA-125 level after six courses was divided into two groups with a CA-12535 U/mL, aneuploidy and mean value of SPF were increased significantly in CA-125>35 U/mL (p=0.05, 0.04). In 2-year survival, CA-125>35 U/mL, aneuploidy and SPF>10% were poor prognostic parameters. CONCLUSION: CA-125 is an important prognostic factor in ovarian cancer. Our results were consistent with the concept that aneuploidy or high percentage of SPF could predict the poor prognosis of disease course. The flow cytometric DNA quantification in ovarian cancer may provide major information about tumor prognosis.