Journal of Clinical Oncology, Vol 16, 1861-1868, Copyright © 1998 by American Society of Clinical Oncology
Ascitic interleukin-12 is an independent prognostic factor in ovarian cancer
AG Zeimet, M Widschwendter, C Knabbe, D Fuchs, M Herold, E Muller-Holzner, G Daxenbichler, FA Offner, O Dapunt and C Marth
Department of Obstetrics and Gynecology, University Hospital, University of Innsbruck, Austria. alain.zeimet@uibk.ac.at
PURPOSE: The clinical impact of endogenous cytokines supplied with
deterministic properties in the generation of either T helper (Th)1 - type
or Th2-type immune response was investigated in patients with ovarian
cancer. Whereas interleukin (IL)- 12 initiates the differentiation of naive
Th0 cells toward Th1 phenotype, IL-4 and IL-10 mediate the development of
Th2-type immunity. PATIENTS AND METHODS: Cytokines were determined before
treatment by means of enzyme-linked immunosorbent assay (ELISA) in ascites
fluid and serum of 76 patients with ovarian cancer. Cytokine levels were
compared with each other and with standard clinicopathologic parameters. A
stepwise logistic regression was calculated to rule out interdependence in
the associations of the various variables. Survival analyses were performed
with the Kaplan-Meier method and differences in survival were examined
according to Mantel and Breslow. Cox proportional hazards analysis was used
to identify independent prognostic factors. RESULTS: Whereas IL-10 and
IL-12 were detectable in all ascites-fluid samples, IL-4 was measurable in
only 43% of the specimens. With the exception of neopterin, macrophage
colony-stimulating factor (M-CSF), and IL-4, determined cytokine levels
were significantly elevated in ascites fluid compared with serum (P <
.01). In univariate analyses, high ascitic- fluid concentrations of either
neopterin, tumor necrosis factor-alpha (TNF-alpha), or IL-12 were
associated with poor disease-free (P < .005) and overall (P < .01)
survival. Multivariate Cox regression analysis showed ascitic-fluid IL-12
levels to be the only immunologic variable that retained independent
prognostic significance (P < .03 for disease- free and P < .01 for
overall survival), together with residual disease, Federation
Internationale de Gynecologie et d'Obstetrique (FIGO)-stage, and patient
age. CONCLUSION: In ovarian cancer, high ascitic-fluid IL- 12 levels, which
may indicate a local Th1-generated immune response, are associated with
disease progression.
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