RESUMO
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 (TAMsIba1) compared with anti-CD68 (TAMsCD68; P<0.001). In central tumour areas and around vessels in the infiltration zone there were more TAMsCD68 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 TAMsCD68 and P<0.001 for TAMsIba1). 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.
RESUMO
BACKGROUND: Glioblastomas are highly aggressive and heterogeneous tumors, both in terms of patient outcome and molecular profile. Magnetic resonance imaging of tumor growth could potentially reveal new insights about tumor biology noninvasively. The aim of this exploratory retrospective study was to investigate the prognostic potential of pretreatment growth rate of glioblastomas, after controlling for known prognostic factors. METHODS: A growth model derived from clinical pretreatment postcontrast T1-weighted magnetic resonance imaging images was used to divide 106 glioblastoma patients into 2 groups. The "faster growth" group had tumors growing faster than expected based on their volume at diagnosis, whereas the "slower growth" group had tumors growing slower than expected. Associations between tumor growth and survival were examined by the use of multivariable Cox regression and logistic regression. RESULTS: None of the known prognostic factors were significantly associated with tumor growth. An extended multivariable Cox model showed that during the first 12 months of follow-up, there was no significant difference in survival between faster and slower growing tumors. Beyond 12 months' follow-up, however, there was a significant, independent survival benefit in having a tumor with slower pretreatment growth. In a multiple logistic regression model including patients receiving both radiotherapy and chemotherapy (n = 82), slower pre-treatment growth of the tumor was shown to be a significant predictor of 2-year survival (odds ratio 4.4). CONCLUSIONS: Pretreatment glioblastoma growth harbors prognostic information. Patients with slower growing tumors have higher odds of survival beyond 2 years, adjusted for other prognostic factors.