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

Shinsuke Kato, Kenji Ishihara, Takao Shinozawa, Hiroyuki Yamaguchi, Yoshiya Asano, Masaya Saito, Masako Kato, Tadashi Terada, Akira Awaya, Asao Hirano, Dennis W. Dickson, Shu Hui Yen, Eisaku Ohama

Research output: Contribution to journalArticlepeer-review

31 Scopus citations


We produced a rat IgG2a monoclonal antibody against the carboxyl terminal region of human midkine (MK), a novel growth factor. This monoclonal antibody was used in immunohistochemical studies to compare the expression of MK, proliferating cell nuclear antigen (PCNA) and p53 protein in 133 primary brain tumors and 21 carcinoma metastases to the central nervous system. Approximately half of the glioblastomas multiforme (GBMs) (19/32), medulloblastomas (8/14), primitive neuroectodermal tumors (PNETs) (5/11), breast carcinoma 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; however, oligodendrogliomas, ependymomas, schwannomas, meningiomas, and pituitary adenomas did not express MK. The values of the PCNA-labeling index were statistically higher in GBMs, medulloblastomas, PNETs, Br-Mts, and L-Mrs that 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 express MK and that the MK expression in brain tumors may depend, in part, on the proliferating potential.

Original languageEnglish (US)
Pages (from-to)430-441
Number of pages12
JournalJournal of Neuropathology and Experimental Neurology
Issue number5
StatePublished - May 1999


  • Brain tumor
  • Glioblastoma multiforme
  • Immunohistochemistry
  • Midkine
  • Monoclonal antibody
  • Proliferating cell nuclear antigen
  • p53 protein

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Neurology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience


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