Characterisation of Tumour Microvessel Density During Progression of High-grade Serous Ovarian Cancer: Clinico-pathological Impact (an OCTIPS Consortium Study)

Background: High-grade serous ovarian cancer (HGSOC) intratumoural vasculature evolution remains unknown. The study investigated changes in tumour microvessel density (MVD) in a large cohort of paired primary and recurrent HGSOC tissue samples and its impact on patients' clinico-pathological outcome.

Methods: A total of 222 primary (pOC) and recurrent (rOC) intra-patient paired HGSOC were assessed for immunohistochemical expression of angiogenesis-associated biomarkers (CD31, to evaluate MVD, and VEGF-A). Expression profiles were compared between pOCs and rOCs and correlated with patients' data.

Results: High intratumoural MVD and VEGF-A expression were observed in 75.7% (84/111) and 20.7% (23/111) pOCs, respectively. MVD and VEGF samples were detected in 51.4% (57/111) and 20.7% (23/111) rOCs, respectively. MVD/VEGF co-expression was found in 19.8% (22/111) and 8.1% (9/111) of pOCs and rOCs, respectively (p = 0.02). Pairwise analysis showed no significant change in MVD (p = 0.935) and VEGF-A (p = 0.121) levels from pOCs to rOCs. MVD pOCs were associated with higher CD3 (p = 0.029) and CD8 (p = 0.013) intratumoural effector TILs, while VEGF samples were most frequently encountered among BRCA-mutated tumours (p = 0.019). Multivariate analysis showed VEGF and MVD were not independent prognostic factors for OS.

Conclusions: HGSOC intratumoural vasculature did not undergo significant changes during disease progression. High concentration of CD31 vessels seems to promote recruitment of effector TILs. The study also provides preliminary evidence of the correlation between VEGF-positivity and BRCA status.