Annals of Oncology 5:627-634, 1994
© 1994 European Society for Medical Oncology
research-article |
Cell kinetics of human ovarian cancer with in vivo administration of bromodeoxyuridine
1Istituto di Ricerche Farmacologiche ‘Mario Negri’ Milano
2Clinica Medico II San Matteo, Pavia
3Anatomia Patologica, Università e I.R.C.C.S. San Matteo, Pavia
4Centra Studi Istochimica C.N.R. Pavia
5Clinica Ostetrica e Ginecologica, Università di Milano Ospedale San Gerardo, Monza
6Clinica Ostetrica e Ginecologica, Università di Pavia Ospedale di Circolo di Varese
7Clinica Ostetrica e Ginecologica Università e I.R.C.C.S. San Matteo, Pavia, Italy
Correspondence to: Eugenio Erba, Istituto di Ricerche Farmacologiche ‘Mario Negri’ Via Eritrea 62, 1-20157 Milan, Italy
BACKGROUND:: Cell kinetics could have prognostic significance in human ovarian cancer and might also help in designing optimal therapy. No data are available on the in vivo kinetics of this tumor using bromodeoxyuridine (BrdU) infusion before surgery.
PATIENTS AND METHODS:: The kinetic parameters of human ovarian carcinoma were investigated in vivo using BrdU incorporation and bivariate BrdU/DNA flow cytometric (FCM) analysis. Fifty-five previously untreated patients with ovarian cancer (F.I.G.O. clinical stage III and IV) were studied. BrdU (250 mg/sqm) was given i.v. 6 h before surgery and samples of primary tumor and metastasis biopsies were fixed in 70/ ethanol. By coupling the BrdU immunoreaction 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 obtained. BrdU immunodetection was done on histological sections of the same tumors.
RESULTS:: The majority of the tumors had a DNA aneuploid content (71.5%). The amount of BrdU-positive S-phase cells varied in different 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% using FCM and 7.2% on visual count of the slide. The mean TS and Tpot were 14.7 h and 12.5 days, respectively. LI and TS were not correlated with 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 was significantly associated with the response after first-line chemotherapy (p < 0.009). In multivariate analysis only residual tumor size was related to the response.
CONCLUSION:: Although this in vivo BrdU technique provides information on the kinetic features of human ovarian cancers, it remains questionable whether this informatiotional value compared to currently used prognostic factors which are assessable clinically and surgically.
ovarian cancer, potential doubling time (Tpot), bromodeoxyuridine, flow cytometry