Ascitic interleukin-12 is an independent prognostic factor in ovarian cancer.
OBJECTIVE
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.


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, Fédération Internationale de Gynécologie et d'Obstétrique (FIGO)-stage, and patient age.


CONCLUSIONS
In ovarian cancer, high ascitic-fluid IL-12 levels, which may indicate a local Th1-generated immune response, are associated with disease progression.
Zeimet
A G
AG
Department of Obstetrics and Gynecology, University Hospital, University of Innsbruck, Austria. alain.zeimet@uibk.ac.at
Widschwendter
M
M
Knabbe
C
C
Fuchs
D
D
Herold
M
M
Müller-Holzner
E
E
Daxenbichler
G
G
Offner
F A
FA
Dapunt
O
O
Marth
C
C
D000328:Adult; D000368:Aged; D001202:Ascitic Fluid / Q000737:chemistry*; D014408:Biomarkers, Tumor / Q000032:analysis*; D018572:Disease-Free Survival; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D016753:Interleukin-10 / Q000032:analysis / Q000097:blood; D018664:Interleukin-12 / Q000032:analysis* / Q000097:blood; D015847:Interleukin-4 / Q000032:analysis; D016173:Macrophage Colony-Stimulating Factor / Q000032:analysis; D008875:Middle Aged; D019798:Neopterin / Q000032:analysis; D010051:Ovarian Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000401:mortality; D011379:Prognosis; D015996:Survival Rate; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D014408:Biomarkers, Tumor; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D018664:Interleukin-12; D015847:Interleukin-4; D019798:Neopterin; D016173:Macrophage Colony-Stimulating Factor