Treatment Strategies Based on Histological Targets against Invasive and Resistant Glioblastoma
Figure 4
Representative histomorphological features of “Go or Grow” in GBM. The two subpopulations consist of uncontrolled-proliferating and abnormally migrating cells which interact mutually, which is so-called ‘‘Go or Grow’’ in gliomas. One subpopulation, rapidly proliferating cells, forms tumor mass being stationary (a, c, e). The other subpopulation, actively migrating cells, moves into surrounding brain without cell division (b, d, f). (a, b) Hematoxylin and eosin staining. (c, d) Immunohistochemistry for Ki-67 antigen, a marker of proliferating cells. The Ki-67 positive cells showing dark brown cell nuclei are detected as proliferating cells. (e, f) Immunohistochemistry for oligodendrocyte transcription factor (OLIG2), which is expressed universally in GBM cell nuclei. Vascular cells in GBM (observed in (e)) and normal glia cells (observed in (f)) are negative for OLIG2. Note that only one Ki-67 positive cell is detected in migrating GBM cells (arrow in (d)), whereas many OLIG2 positive GBM cells are seen in the same area (f). Also note that the sizes of cell nuclei recognized in (f) are smaller than that in (e). This means that migrating GBM cells into surrounding brain have smaller nuclei because they are actively moving. Scale bars, 100 μm.