Histological Characterization of the Tumorigenic “Peri-Necrotic Niche” Harboring Quiescent Stem-Like Tumor Cells in Glioblastoma
Fig 3
SOX2+ (or NANOG+) HIF-1α+ RNApII-S2P-/low tumor cells are not found in zones around small pseudopalisading necroses or in areas showing no necrotic change.
These cells are found in glioblastomas (WHO grade IV), but not in diffuse astrocytomas (grade II) and anaplastic astrocytomas (grade III). a, b: Serial sections of glioblastoma tissue containing small pseudopalisading necroses. c, d: Serial sections of glioblastoma tissue showing no necrotic changes. H-E staining (a, c) and triple immunostaining for SOX2/HIF-1α/RNApII-S2P (b, d) are shown. Although SOX2+ and/or HIF-1α+ tumor cells were found, they were RNApII-S2P+. Therefore, SOX2+ HIF-1α+ RNApII-S2P-/low cells were not observed. NS, small pseudopalisading necrosis; V, blood vessel. Scale bars, 50 μm. e: Triple immunostaining for SOX2/HIF-1α/RNApII-S2P in astrocytomas of WHO grade II and III. No SOX2+ HIF-1α+ RNApII-S2P-/low cells were observed. Scale bars, 25 μm. f, g: Frequency of SOX2+ HIF-1α+ RNApII-S2P-/low cells (f) and NANOG+ HIF-1α+ RNApII-S2P-/low cells (g) in cases of astrocytic tumors of WHO grade II–IV. *, P < 0.05; **, P < 0.01 (grade IV vs. combined group of grades II and III).