Abstract
BackgroundHigh-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.MethodsA 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.ResultsHigh intratumoural MVD and VEGF-A expression were observed in 75.7% (84/111) and 20.7% (23/111) pOCs, respectively. MVDhigh and VEGF(+) samples were detected in 51.4% (57/111) and 20.7% (23/111) rOCs, respectively. MVDhigh/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. MVDhigh 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.ConclusionsHGSOC 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.
Highlights
High-grade serous ovarian carcinoma (HGSOC) still accounts for the highest mortality rate among all ovarian cancer (OC) histotypes, with almost 80% of all new deaths from OC being caused by this distinct subgroup of ovarian tumours.[1,2,3,4] International groups of opinion leaders have recognised the designing of new translational studies on recurrent and end-stage HGS tumour tissue samples as a key 'unmet need' in the understanding of High-grade serous ovarian cancer (HGSOC) biology and clonal evolution.[4]In this scenario, analysis of the evolution process affecting intratumoural vasculature during HGSOC progression is a pivotal issue to be still elucidated
A total of 222 intra-patient paired primary and recurrent HGSOC tissue samples derived from 111 patients were included
microvessel density (MVD) staining MVDhigh staining was detected in 75.7% (84/111) of pos coexpression (pOC) and in 51.4% (57/111) of rOC, whereas MVDlow staining was found in 24.3% (27/111) and in 48.6% (54/111) of pOC and rOC, respectively
Summary
High-grade serous ovarian carcinoma (HGSOC) still accounts for the highest mortality rate among all ovarian cancer (OC) histotypes, with almost 80% of all new deaths from OC being caused by this distinct subgroup of ovarian tumours.[1,2,3,4] International groups of opinion leaders have recognised the designing of new translational studies on recurrent and end-stage HGS tumour tissue samples as a key 'unmet need' in the understanding of HGSOC biology and clonal evolution.[4] In this scenario, analysis of the evolution process affecting intratumoural vasculature during HGSOC progression is a pivotal issue to be still elucidated. The study provides preliminary evidence of the correlation between VEGF-positivity and BRCA status
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