Overexpression of both vascular endothelial growth factor (VEGF) and a natural antisense form of hypoxia-inducible factor 1α (aHIF) is associated with decreased metastasis-free survival in patients with paraganglioma (PGL), according to a study conducted at Radboud University Nijmegen Medical Centre, The Netherlands.

Paul Span and his research team set out to investigate the role of hypoxia-induced gene expression, in particular aHIF, on disease progression. Frozen tumor tissue collected from 87 patients with PGL enabled Span and colleagues to correlate the expression of aHIF and VEGF, as assessed by quantitative RT-PCR, with tumor subtypes characterized by specific germline mutations and with disease prognosis, after a follow-up period of up to 21 years. The results indicated that aHIF and VEGF are overexpressed in PGLs with a hypoxic-like phenotype that results from mutations in SDH and/or VHL.

Patients with increased VEGF and aHIF expression had significantly reduced metastasis-free survival, indicating that overexpression of these genes could be a marker of PGL virulence. As Span explains, metastases develop in 10–15% of PGLs and often occur decades after primary treatment, which requires long-term indiscriminate patient follow-up. The identification of biomarkers of PGL aggressiveness could facilitate targeted selection of patients for intensive follow-up. “Identifying the mechanisms associated with or involved in disease progression could offer new targets for therapy or metastasis prevention,” he adds.