gms | German Medical Science

Objective: There are only anecdotal reports on metastatic glioblastoma (GBM), mostly in the context of organ transplantation. To explore the possibility that the true occurrence of GBM cells circulating in the blood might be higher than anticipated but metastasis does not occur for reasons offering clues to the extracranial control of this disease, we used established methods to detect circulating tumor cells in metastatic disease to search for such circulating tumor cells (CTCs).

Method: The peripheral blood taken preoperatively (10ml) from 141 glioblastoma patients was screened for the presence of GFAP positive mononuclear cells with automatized methods to detect circulating tumor cells.

Results: In 29 patients (20.6%) such cells were found. By screening three slides of mononuclear spreads per case containing 2.1 x 106 cells, positive cells were found at a rate of 1 to 22 cells per positive patient. Such cells showed chromosomal aberrations typical for GBM (gains of chromosome 7 and loss of PTEN). Additional mutations of two other genes, MYH11 and MECOM were found with yet undetermined biological significance, possibly relevant in epithelial-mesenchymal transition. CTSs appeared to be more frequent in patients with EGF-R amplified tumors. Clinically no correlation with survival was seen, no patient surviving longer than 2 yrs had clinical evidence of metastasis.

Conclusions: CTSs are present in glioblastoma patients much more frequently than expected. Lack of any clinical correlate except in immuno-suppressed organ recipients from glioblastoma patients point towards an effective immunresponse outside the brain. The mechanisms leading to effective control of GBM cells in the extracranial environment may harbour therapeutic opportunities beyond the traditional oncological therapies.