Monoclonal antibody to human midkine reveals increased midkine expression in human brain tumors

We produced a rat IgG2a monoclonal antibody against the carboxyl terminal r egion of human midkine (MK), a novel growth factor. This monoclonal antibod y was used in immunohistochemical studies to compare the expression of MK, proliferating cell nuclear antigen (PCNA) and p53 protein in 133 primary br ain tumors and 21 carcinoma metastases to the central nervous system. Appro ximately half of the glioblastomas multiforme (GBMs) (19/32), medulloblasto mas (8/14), primitive neuroectodermal tumors (PNETs) (5/11), breast carcino ma metastases (Br-Mts) (6/10) and lung carcinoma metastases (L-Mts) (5/11) as well as some astrocytomas (2/14) had tumor cells that expressed MK: howe ver, oligodendrogliomas,ependymomas, schwannomas, meningiomas, and pituitar y adenomas did not express MK. The values of the PCNA-labeling index were s tatistically higher in GBMs, medulloblastomas, PNETs, Br-Mts, and L-Mts tha t expressed MK than in those that did not (Wilcoxon rank-sum test, p < 0.05 ). There was no correlation between MK and p53 protein in all tumor types. Normal and non-neoplastic brain tissues were negative for MK, PCNA, and p53 protein. We conclude that primary and metastatic tumors of the brain expre ss MK and that the MK expression in brain tumors may depend, in part, on th e proliferating potential.