Immunohistochemical expression of inducible nitric oxide synthase (iNOS) in human brain tumors: Relationships of iNOS to superoxide dismutase (SOD) proteins (SOD1 and SOD2), Ki-67 antigen (MIB-1) and p53 protein

Shinsuke Kato, Hiroyasu Esumi, Asao Hirano, Masako Kato, Kohtaro Asayama, Eisaku Ohama

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In this study, inducible nitric oxide synthase (iNOS) expression in a series of 158 human primary brain tumors was analyzed. To gain some insight into the biological significance of iNOS expression in tumor cells, comparative immunohistochemical analyses were employed to characterize the expression of iNOS, superoxide dismutase (SOD) proteins (SOD1 and SOD2), Ki-67 antigen (MIB-1) and p53 protein in these cells. Sixteen (39.0%) of the 41 glioblastoma multiforme (GBM) specimens showed iNOS immunoreactivity. Positive immunoreactions with iNOS were also detected in 2/8 anaplastic astrocytomas, 1/17 astrocytomas, 1/14 medulloblastomas and 1/11 primitive neuroectodermal tumors, but no positive reactions were observed in oligodendrogliomas (0/11), ependymomas (0/5), schwannomas (0/21), meningiomas (0/23) or pituitary adenomas (0/7). The MIB-1 labeling index of GBMs that expressed iNOS was significantly higher than that of GBMs that did not (0.025< P <0.05, Wilcoxon rank-sum test). Unlike iNOS-negative tumors, all iNOS-positive tumors coexpressed SOD1 or SOD2. In particular, there was a significant correlation between iNOS induction and SOD1 expression (P =1.65×10-10, Fisher's exact test) in GBM specimens. There was no significant relationship between iNOS and p53 protein in any type of primary brain tumor (P >0.05, Fisher's exact test). No significant immunohistochemical reactions with iNOS, MIB-1 or p53 protein were observed in normal brain tissue sections. We conclude that primary brain tumors express iNOS, and that iNOS expression in brain tumor cells may depend, in part, on cellular proliferation potential. Based on the fact that SOD1 scavenges oxidative-stress species originating from large amounts of nitric oxide (NO) produced by iNOS, iNOS-expressing brain tumor cells may protect themselves against NO cytotoxicity by overinducing SOD1.

Original languageEnglish (US)
Pages (from-to)333-340
Number of pages8
JournalActa neuropathologica
Issue number4
StatePublished - Apr 1 2003



  • Brain tumor
  • Inducible nitric oxide synthase
  • Ki-67 antigen (MIB-1)
  • P53 protein
  • Superoxide dismutase proteins (SOD1 and SOD2)

ASJC Scopus subject areas

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

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