Microglia and macrophages in human glioblastomas: A morphological and immunohistochemical study

Glioblastomas (GBMs), a type of highly malignant brain tumour, contain various macrophages/microglia that are known as tumour-associated macrophages (TAMs). These TAMs have various roles in tumour biology. Histopathological aspects of TAMs and associations with tumour growth assessed by magnetic resonance imaging (MRI) are poorly described. In the present study, 16 patients that had sufficient tumour tissue and histological hallmarks were examined. The tumours were classified as either slow- (n=7) or fast-growing (n=9) based on the segmented tumour volumes from MRI scans taken at diagnosis and preoperatively. Using cluster of differentiation (CD)68 and ionized calcium-binding adaptor molecule 1 (Iba1) antibodies, the number, morphology, localization and distribution of TAMs in the GBM tissue were studied. TAMs were significantly more immunoreactive for anti-Iba1 (TAMs(Iba1)) compared with anti-CD68 (TAMs(CD68); P<0.001). In central tumour areas and around vessels in the infiltration zone there were more TAMs(CD68) in slow-growing tumours (P=0.003 and P=0.025, respectively). Central tumour areas contained more TAMs compared with the infiltration zone (P=0.001 for TAMs(CD68) and P<0.001 for TAMs(Iba1)). The majority of TAMs exhibited a ramified phenotype in the infiltration zone, whereas central TAMs were mostly amoeboid. TAMs were present in high numbers in most regions of the tumour, whereas there were few in necrotic areas. In conclusion, the present study demonstrated and confirmed that the high numbers of TAMs in GBMs assume a range of morphologies consistent with various activation states, and that slow-growing GBMs seem to contain a TAM-population different to their fast-growing counterparts.