Background and Aim: Blockade of CD95/CD95 ligand (CD95 L) signaling is a promising therapeutic approach for the treatment of glioblastoma (GBM), while methylation of a single cytosine-phosphate-guanine site (CpG2) upstream of the CD95 L promoter has been identified as a prognostic biomarker for GBM. Here, we conducted the first investigation of CD95 L expression and CpG2 methylation levels in the CD95 L promoter in GBM patients. Materials and Methods: In this observational study, tissue samples were collected from 69 patients with a primary diagnosis of World Health Organization Grade IV GBM treated at the Department of Glioma Surgery, Huashan Hospital, Shanghai Medical College, Fudan University and tested for CD95 L expression using immunohistochemistry (IHC). The CpG2 methylation status of the samples was also evaluated, and its impact on overall survival (OS) was assessed by univariate analysis. The study was approved by the Hospital Institutional Review Board (approval No. 220) on July 7, 2015. Results: The IHC results showed a CD95 L detection rate of at least 43.5% for tissue samples with IHC scores of 2⁺ or 3⁺ and 78.3% for those with IHC scores of 1⁺, 2⁺, or 3⁺. Patients with high CpG2 methylation levels (≥52% higher than the median value; n = 32) had significantly longer median survival compared with those with low CpG2 methylation levels (n = 29) (22.95 vs. 14.5 months; P = 0.0084). GBM patients who underwent gross total tumor resection (n = 57) showed similar results. Those in the high CpG2 methylation group had longer median OS compared with that of patients in the low CpG2 methylation group (23.5 vs. 18.0 months; P = 0.0141). Conclusions: Our results showed a significant prevalence of CD95 L expression in GBM patients, whereas CpG2 hypermethylation within the CD95 L promoter was positively associated with survival. These findings support that CD95/CD95 L signaling blockade has potential as a therapeutic strategy targeting treatment-resistant GBM.

Although it is well known that 49% cases of upper limb deep-vein thrombosis are due to malignancies and the likelihood of venous thromboembolism is increased in patients with high grade gliomas due to the heightened prothrombotic milieu, requisite preoperative laboratory coagulation studies are not performed routinely in these patients to decide whether appropriate antithrombotic medications are required preoperatively. In addition, it is controversial whether antithrombotic therapy should be initiated before neurosurgery in view of the risk of intraoperative bleeding. Here, we have described the case of a 29-year-old female with high grade frontal malignant astrocytoma who developed the extremely rare complication of upper limb compartment syndrome postoperatively. The patient had no history of thrombotic events, and her basic laboratory parameters were not deranged in the pre-operative period. This rare case, supported with a literature review, suggested that the risk of thrombosis is increased in high grade and large gliomas, making us rethink the overall battery of investigations and perioperative medical management of such cases. We strongly recommend peri-operative coagulation studies and appropriate antithrombotic measures along with vigilant perioperative monitoring to avoid thrombotic complication in this subset of patients.