Circulating endothelial cells and procoagulant microparticles in patients with glioblastoma: prognostic value.
OBJECTIVE
Circulating endothelial cells and microparticles are prognostic factors in cancer. However, their prognostic and predictive value in patients with glioblastoma is unclear. The objective of this study was to investigate the potential prognostic value of circulating endothelial cells and microparticles in patients with newly diagnosed glioblastoma treated with standard radiotherapy and concomitant temozolomide. In addition, we have analyzed the methylation status of the MGMT promoter.


METHODS
Peripheral blood samples were obtained before and at the end of the concomitant treatment. Blood samples from healthy volunteers were also obtained as controls. Endothelial cells were measured by an immunomagnetic technique and immunofluorescence microscopy. Microparticles were quantified by flow cytometry. Microparticle-mediated procoagulant activity was measured by endogen thrombin generation and by phospholipid-dependent clotting time. Methylation status of MGMT promoter was determined by multiplex ligation-dependent probe amplification.


RESULTS
Pretreatment levels of circulating endothelial cells and microparticles were higher in patients than in controls (p<0.001). After treatment, levels of microparticles and thrombin generation decreased, and phospholipid-dependent clotting time increased significantly. A high pretreatment endothelial cell count, corresponding to the 99(th) percentile in controls, was associated with poor overall survival. MGMT promoter methylation was present in 27% of tumor samples and was associated to a higher overall survival (66 weeks vs 30 weeks, p<0.004).


CONCLUSIONS
Levels of circulating endothelial cells may have prognostic value in patients with glioblastoma.
Servicio de Oncología Médica, Hospital Universitari i Politècnic La Fe, Valencia, Spain. greynesm@gmail.com
Gaspar
G
Reynés
Virtudes
V
Vila
Tania
T
Fleitas
Edelmiro
E
Reganon
Jaime
J
Font de Mora
María
M
Jordá
Vicenta
V
Martínez-Sales
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood; D001777:Blood Coagulation; D001932:Brain Neoplasms / Q000097:blood* / Q000473:pathology*; D016022:Case-Control Studies; D055252:Cell-Derived Microparticles / Q000378:metabolism*; D015254:DNA Modification Methylases / Q000235:genetics; D045643:DNA Repair Enzymes / Q000235:genetics; D042783:Endothelial Cells / Q000473:pathology*; D005260:Female; D005909:Glioblastoma / Q000097:blood* / Q000473:pathology*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016896:Treatment Outcome; D025521:Tumor Suppressor Proteins / Q000235:genetics
D014408:Biomarkers, Tumor; D025521:Tumor Suppressor Proteins; D015254:DNA Modification Methylases; C515491:MGMT protein, human; D045643:DNA Repair Enzymes