Endoglin (CD105) and proliferation index in recurrent glioblastoma treated with anti-angiogenic therapy

Abstract

Introduction: CD105 is an angiogenic biomarker whose expression has inconsistent effects in the prognosis of GBM patients. We aimed to evaluate the prognostic impact of CD105 and proliferation index in primary and recurrent tumoral specimens of a cohort of GBM patients treated with bevacizumab upon recurrency. Materials and Methods: We conducted a retrospective study of 102 consecutive GBM patients treated with anti-angiogenic upon recurrence at CHUSJ between 2010 and 2017. Demographic, clinical and survival data of all patients were collected and analysed. Tissue expression of Ki-67 and CD105 in primary and recurrent specimens was correlated with progression-free survival after temozolomide (PFS-1), progression free survival after bevacizumab (PFS-2) and overall survival (OS). Results: Mean microvessel density (MVD)-CD105 expression in primary tumours was 15.42 (Standard Deviation - SD:9.84). Furthermore, in the recurrent tumours (n=16) the mean MVD-CD105 expression was 16.49 (SD:12.56). Mean Ki-67 expression was 31 % (SD:17.32%) in primary tumors and 29% (SD:10.30%) at recurrence. MVD-CD105 expression in the primary tumor had no impact in PFS-1, PFS-2 or OS. At recurrence, patients with increased MVD-CD105 were associated with a worse median PFS-2 (2 vs 8 months; p=0.045) and OS (17 vs 26 months; p=0.007) compared to those with lower MVD-CD105, respectively. CD105 tumoral pattern and localization showed no impact on prognosis. Mitotic index was not associated with differences in survival outcomes. Conclusion: In this study, higher MVD-CD105 in recurrent tumoral specimens of recurrent GBM patients seems to be associated with a worse PFS-2 and OS, while portending no prognostic significance in the primary setting.