Endogenous interleukin-12: Relationship with angiogenic factors, hormone receptors and nodal status in human breast carcinoma

Interleukin-12 (IL-12) is known to be a key cytokine for regulating immune response, but it is also known to provide some other biological function in cluding inhibition of angiogenesis. We have determined using an enzymatic i mmunoassay the endogenous levels of IL-12 in 390 cytosols of primary breast cancers previously tested also for the angiogenic peptides, vascular endot helial growth factor (VEGF) and thymidine phosphorylase (TP). The concentra tion of IL-12 ranged from 0 to 7.6 ng/mg protein, and 124 (31.8%) out of 39 0 cancers showed a detectable dose (>0.1 ng/ml). There was no statistical a ssociation of IL-12 levels with tumor size and menopausal status. IL-12 lev els tended to be higher in the tumors of node-positive patients as compared to those of node-negative ones (t-test, p=0.082). In addition, IL-12 level s were inversely associated with hormone receptor status, particularly prog esterone receptor expression (p=0.0013). There was a significant inverse as sociation between IL-12 and TP concentration (p=0.0007). The proportion of tumors with detectable levels of IL-12 and low levels of either VEGF or TP was higher among the patients with node-negative as compared to those with node-positive disease. On the contrary, the proportion of tumors with no de tectable IL-12 and high levels of either VEGF or TP was higher in node-posi tive versus node-negative cancers. In conclusion, our study evaluated the b alance between pro-angiogenic factors (TP and VEGF) and IL-12, as a detecta ble naturally occurring inhibitor of angiogenesis, in the same series of no de-negative and node-positive breast cancers. Further studies are warranted to investigate the biological and clinical significance of the co-determin ation of pro and contra angiogenic factors in human breast carcinoma.