Vascular endothelial growth factor: A potential prognosticator in Ewing sarcoma

Vascular endothelial growth factor (VEGF) is an angiogenic marker and is implicated in the carcinogenesis and prognostication of cancers. However, its prognostic potential in Ewing sarcoma (ES) merits exploration.

Histopathologically confirmed consecutive ES cases registered at our institute from 2014 to 2018 were analyzed. Immunohistochemical staining for VEGF was performed on tumor tissues, and they were further classified based on VEGF intensity.

There were 105 patients (53 non-metastatic and 52 metastatic). VEGF immunostaining in non-metastatic and metastatic cohorts was negative in 20 (37.7%) and 21 (40.4%), mildly positive in 13 (24.5%) and 9 (17.3%) cases, moderately positive in 14 (26.4%) and 16 (30.8%), and was intensely positive in 6 (11.3%) and 7 (13.5%) patients, respectively. VEGF immunoexpression of up to 25% was seen in 14 (13.3%) and 10 (9.5%) patients within the non-metastatic and metastatic cohorts, respectively. For the non-metastatic cohort, the median EFS (months) was 78.6 (95% CI: 61.34-NA), whereas the median OS was not reached. The median EFS and OS (months) were 10.8 (95% CI: 6.41-17.1) and 13.5 (95% CI: 8.08-21.2), respectively, for the metastatic cohort. Metastatic ES patients having either VEGF immunostaining in >25% of tumor cells or moderate/strong immunostaining were found to have inferior OS (P = 0.008, HR = 10.565). In addition, metastatic patients who were treatment naïve had inferior OS, whereas patients who underwent definitive surgery and completed treatment had superior OS (P = 0.003, P = 0.015, and P = 0.009, respectively).

VEGF was found to be an independent prognostic marker in metastatic ESs. This may translate to therapeutic relevance but needs validation in the subsequent, larger prospective studies.