Copper/zinc superoxide dismutase, nuclear DNA content, and progression in human gliomas

To our knowledge, there have been no previous reports regarding the immunohistochemistry and image cytometry to demonstrate elevated Copper/zinc superoxide dismutase (Cu/Zn SOD) expression and numbers of the clonal cells in human gliomas. In 30 well-studied patients with gliomas, immunoreactivity for Cu/Zn SOD and cytometric evidence of DNA ploidy in the G2M cell cycle phase were evaluated from routinely prepared tissue blocks. Cu/Zn SOD positive tumor cells were shown in 8 of 13 glioblastomas (mean quantitative immunoreactivity SOD score; 1), 3 of 8 anaplastic gliomas (score; 0.6), and none of 9 low-grade gliomas. The differences in SOD score was not significant. In hypertetraploid glioblastomas, time to progression was shorter than for hypertetraploid of anaplastic gliomas, while SOD scores were not significantly different. The same relationship held for tetraploid specimens. Considering variables in combination, hypertetraploid gliomas with high SOD immunoreactivity showed a significantly short time to progression (p < 0.05) (1-5 months after radiotherapy and chemotherapy) compared with hypertetraploid, low-SOD immunoreactivity gliomas or tetraploid, low-SOD immunoreactivity gliomas. The tumor cells with high SOD activity also tended to be resistant for radiotherapy and anticancer drugs. Those results were suggested that the high grade glioma with a single clone and low SOD activity were effective for radiotherapy associated with oxidative stress, and that the high grade gliomas with more than two clones and high SOD activity were very less effective for same therapy. Cu/Zn SOD activity and the degree of the clonality in human gliomas should be very important factors influencing a choice of oxidative cytotoxic treatment.