Cell kinetics of human ovarian cancer with in vivo administration of bromodeoxyuridine

E. Erba, M. Giordano, M. Danova, G. Mazzini, P. Ubezio, V. Torri, C. Mangioni, F. Landoni, P. Bolis, P. Tenti, M. Franchi, L. Babilonti, A. Riccardi, M. D'Incalci

Research output: Contribution to journalArticle

Abstract

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 an 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 information has any additional value compared to currently used prognostic factors which are assessable clinically and surgically.

Original languageEnglish
Pages (from-to)627-634
Number of pages8
JournalAnnals of Oncology
Volume5
Issue number7
Publication statusPublished - 1994

Fingerprint

Ovarian Cancer
Bromodeoxyuridine
Ovarian Neoplasms
Tumors
Tumor
Kinetics
Cell
Neoplasms
Residual Neoplasm
S Phase
DNA
Ploidies
Labeling
Surgery
Human
Cancer
Aneuploidy
Prognostic Factors
Chemotherapy
Metastasis

Keywords

  • Bromodeoxyuridine
  • Flow cytometry
  • Ovarian cancer
  • Potential doubling time (Tpot)

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Statistics, Probability and Uncertainty
  • Applied Mathematics
  • Public Health, Environmental and Occupational Health
  • Neuropsychology and Physiological Psychology
  • Hematology

Cite this

Cell kinetics of human ovarian cancer with in vivo administration of bromodeoxyuridine. / Erba, E.; Giordano, M.; Danova, M.; Mazzini, G.; Ubezio, P.; Torri, V.; Mangioni, C.; Landoni, F.; Bolis, P.; Tenti, P.; Franchi, M.; Babilonti, L.; Riccardi, A.; D'Incalci, M.

In: Annals of Oncology, Vol. 5, No. 7, 1994, p. 627-634.

Research output: Contribution to journalArticle

Erba, E, Giordano, M, Danova, M, Mazzini, G, Ubezio, P, Torri, V, Mangioni, C, Landoni, F, Bolis, P, Tenti, P, Franchi, M, Babilonti, L, Riccardi, A & D'Incalci, M 1994, 'Cell kinetics of human ovarian cancer with in vivo administration of bromodeoxyuridine', Annals of Oncology, vol. 5, no. 7, pp. 627-634.
Erba, E. ; Giordano, M. ; Danova, M. ; Mazzini, G. ; Ubezio, P. ; Torri, V. ; Mangioni, C. ; Landoni, F. ; Bolis, P. ; Tenti, P. ; Franchi, M. ; Babilonti, L. ; Riccardi, A. ; D'Incalci, M. / Cell kinetics of human ovarian cancer with in vivo administration of bromodeoxyuridine. In: Annals of Oncology. 1994 ; Vol. 5, No. 7. pp. 627-634.
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abstract = "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 an 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 information has any additional value compared to currently used prognostic factors which are assessable clinically and surgically.",
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T1 - Cell kinetics of human ovarian cancer with in vivo administration of bromodeoxyuridine

AU - Erba, E.

AU - Giordano, M.

AU - Danova, M.

AU - Mazzini, G.

AU - Ubezio, P.

AU - Torri, V.

AU - Mangioni, C.

AU - Landoni, F.

AU - Bolis, P.

AU - Tenti, P.

AU - Franchi, M.

AU - Babilonti, L.

AU - Riccardi, A.

AU - D'Incalci, M.

PY - 1994

Y1 - 1994

N2 - 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 an 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 information has any additional value compared to currently used prognostic factors which are assessable clinically and surgically.

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