CELL-KINETICS OF HUMAN OVARIAN-CANCER WITH IN-VIVO ADMINISTRATION OF BROMODEOXYURIDINE

Background: Cell kinetics could have prognostic significance in human ovarian cancer and might also help in designing optimal therapy. No da ta are available on the in vivo kinetics of this tumor using bromodeox yuridine (BrdU) infusion before surgery. Patients and methods: The kin etic parameters of human ovarian carcinoma were investigated in vivo u sing BrdU incorporation and bivariate BrdU/DNA flow cytometric (FCM) a nalysis. Fifty-five previously untreated patients with ovarian cancer (F.I.G.O. clinical stage III and IV) were studied. BrdU (250 mg/sqm) w as given i.v. 6 h before surgery and samples of primary tumor and meta stasis biopsies were fixed in 70% ethanol. By coupling the BrdU immuno reaction with biparametric FCM analysis, the nuclear DNA content (i.e. , ploidy status), the tumor labelling index (LI), the synthesis time ( TS) and the potential doubling time of the tumor mass (Tpot) were obta ined. BrdU immunodetection was done on histological sections of the sa me tumors. Results: The majority of the tumors had a DNA aneuploid con tent (71.5%). The amount of BrdU-positive S-phase cells varied in diff erent tumor samples and when several samples were taken from the same tumor. The proportion of BrdU-negative S-phase cells was large (50% of the total S phase cells) in almost all cases. The mean LI was 6.1% us ing FCM and 7.2% on visual count of the slide. The mean TS and Tpot we re 14.7 h and 12.5 days, respectively. LI and TS were not correlated w ith clinical tumor stage, histological grading, residual tumor size or DNA ploidy, but Tpot was significantly higher (p < 0.05) in patients with residual tumor size <2 cm. Univariate analysis showed that Tpot w as significantly associated with the response after first-line chemoth erapy (p < 0.009). In multivariate analysis only residual tumor size w as related to the response. Conclusion: Although this in vivo BrdU tec hnique provides information on the kinetic features of human ovarian c ancers, it remains questionable whether this information has any addit ional value compared to currently used prognostic factors which are as sessable clinically and surgically.