Multivariate analysis of the prognostic significance of DNA-ploidy and S-phase fraction in ovarian cancer determined by flow cytometry following detection of cytokeratin-labeled tumor cells.
OBJECTIVE
The outcome of patients with advanced ovarian cancer is poor despite aggressive therapy including surgery and multiagent chemotherapy. Valid prognostic factors are necessary to estimate the course of the disease and to define biologically similar subgroups for analysis of therapeutic efficacy.


METHODS
This study is the first published prospective study concerning the prognostic significance of DNA-ploidy and S-phase fraction in ovarian cancer following enrichment of tumor cells by cytokeratin labeling. Epithelial cells were labeled by FITC-conjugated cytokeratin antibody (CK 5, 6, 8, and 17) prior to flow cytometric cell cycle analysis in 129 fresh specimens of primary ovarian cancer.


RESULTS
Recurrence-free survival of patients with DNA-diploid primary ovarian cancer was significantly better compared to that of patients with DNA-aneuploid tumors in univariate analysis (47% vs 18%, P = 0.01). The tumor-dependent overall survival of patients with DNA-diploid tumors was 57% compared to 30% with DNA-aneuploid tumors (P = 0.04). In FIGO stage III ovarian cancer DNA-ploidy, optimized by cytokeratin gating for tumor cells, achieved independent prognostic significance. No significance was found for S-phase fraction. However, despite convincing methodological advantages in the detection of DNA-aneuploid subpopulations the clinical significance of cytokeratin gating of epithelial cells was only marginal.


CONCLUSIONS
DNA-ploidy has been shown to be as powerful or even more so in comparison to postoperative residual tumor in multivariate analysis for predicting clinical outcome in advanced ovarian cancer. Thus, determination of DNA-ploidy should be introduced to currently recruiting phase III studies for therapy of ovarian cancer for better definition of prognostic subgroups.
Kimmig
Rainer
R
Department of Obstetrics and Gynecology, Ludwig-Maximilians-University, Munich, D-81377, Germany. rainer.kimmig@gyn.med.uni-muenchen.de
Wimberger
Pauline
P
Hillemanns
Peter
P
Kapsner
Thomas
T
Caspari
Claudia
C
Hepp
Hermann
H
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004273:DNA, Neoplasm / Q000032:analysis / Q000235:genetics*; D018572:Disease-Free Survival; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007633:Keratins / Q000378:metabolism*; D008875:Middle Aged; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D011003:Ploidies; D011446:Prospective Studies; D016196:S Phase / Q000502:physiology*
D004273:DNA, Neoplasm; D007633:Keratins