Characterisation of tumour microvessel density during progression of high-grade serous ovarian cancer: clinico-pathological impact (an OCTIPS Consortium study)

Abstract

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^high and VEGF⁽⁺⁾ samples were detected in 51.4% (57/111) and 20.7% (23/111) rOCs, respectively. MVD^high/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^high 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.

Fig. 1

CD31 immunohistochemistry staining for intratumoural MVD assessment: MVD^high (a) and MVD^low (b) pOC samples; MVD^high (c) and MVD^low (d) rOC samples. ×400 magnification; MVD count among primary and recurrent tumours (box plot (e) and scatter plot (f))

Fig. 2

VEGF-A immunohistochemistry staining. VEGF-A IRS distribution in primary (a) and recurrent (d) tumour samples. pOCs, VEGF⁽⁺⁾ (b) and VEGF⁽⁻⁾ (c); rOCs, VEGF⁽⁺⁾ (e) and VEGF⁽⁻⁾ (f); VEGF-A IRS among primary and recurrent tumours (box plot (g) and scatter plot (h))

Fig. 3

MVD and/or VEGF status and progression-free survival after primary (PFI (a), (b), (c)) and recurrent (PFS, (d), (e), (f)) disease. g–i MVD and/or VEGF status at primary disease and overall survival. 'x-axis': months, 'y-axis': survival probability