Factors influencing tumour cell and vascular proliferation in glioblastoma

Introduction:  This project examines the factors that influence tumour cell and vascular proliferation in glioblastomas.
Hypothesis:  Necrosis is a major factor inducing tumour cell and vascular proliferation in glioblastomas.
Material and methods:  5 µm paraffin sections from 10 cases of glioblastoma containing areas of normal brain, viable tumour and necrosis were stained with H&E, reticulin and by immunocytochemistry for GFAP, Ki-67, CD34 for blood vessel endothelium, a combined Ki-67/CD34, and CD68 for macrophages and microglia. Tumour cell proliferation in Ki-67 preparations was measured in relation to (a) distance from necrosis and (b) proximity to blood vessels. The density of blood vessels was related to the distance from necrosis, and the presence of macrophages was related to the distance from necrosis and to the proximity to blood vessels. These measurements were effected by an automated computer quantification algorithm and by field-specific ocular quantification.
Results:  The mean tumour proliferation index (PI) was 6.49% (±4.95), with a two-fold increase in tumour cell PI to 12.36% ± 5.82 ( P  ≤ 0.001) in the vicinity of blood vessels. The density of blood vessels was increased in the vicinity of areas of necrosis. Macrophages were distributed throughout the tumour, but were increased around areas of necrosis and around blood vessels. No relationship between tumour cell proliferation and necrosis was detected.
Conclusions:  Tumour cell proliferation is concentrated around blood vessels in glioblastomas. Blood vessel proliferation, but not tumour cell proliferation, is related to areas of necrosis and the presence of macrophages in glioblastomas. Targeting of blood vessel proliferation and macrophages within glioblastoma may present a therapeutic strategy for treatment of these devastating tumours.