Poor perfusion of the microvasculature in peritoneal metastases of ovarian cancer

Arnoud W. Kastelein*, Laura M.C. Vos, Juliette O.A.M. van Baal, Jasper J. Koning, Vashendriya V.V. Hira, Rienk Nieuwland, Willemien J. van Driel, Zühre Uz, Thomas M. van Gulik, Jacco van Rheenen, Can Ince, Jan Paul W.R. Roovers, Cornelis J.F. van Noorden, Christianne A.R. Lok

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Most women with epithelial ovarian cancer (EOC) suffer from peritoneal carcinomatosis upon first clinical presentation. Extensive peritoneal carcinomatosis has a poor prognosis and its pathophysiology is not well understood. Although treatment with systemic intravenous chemotherapy is often initially successful, peritoneal recurrences occur regularly. We hypothesized that insufficient or poorly-perfused microvasculature may impair the therapeutic efficacy of systemic intravenous chemotherapy but may also limit expansive and invasive growth characteristic of peritoneal EOC metastases. In 23 patients with advanced EOC or suspicion thereof, we determined the angioarchitecture and perfusion of the microvasculature in peritoneum and in peritoneal metastases using incident dark field (IDF) imaging. Additionally, we performed immunohistochemical analysis and 3-dimensional (3D) whole tumor imaging using light sheet fluorescence microscopy of IDF-imaged tissue sites. In all metastases, microvasculature was present but the angioarchitecture was chaotic and the vessel density and perfusion of vessels was significantly lower than in unaffected peritoneum. Immunohistochemical analysis showed expression of vascular endothelial growth factor and hypoxia inducible factor 1α, and 3D imaging demonstrated vascular continuity between metastases and the vascular network of the peritoneum beneath the elastic lamina of the peritoneum. We conclude that perfusion of the microvasculature within metastases is limited, which may cause hypoxia, affect the behavior of EOC metastases on the peritoneum and limit the response of EOC metastases to systemic treatment.

Original languageEnglish
Number of pages12
JournalClinical and Experimental Metastasis
Volume37
Issue number2
DOIs
Publication statusE-pub ahead of print - 1 Jan 2020

Cite this

Kastelein, A. W., Vos, L. M. C., van Baal, J. O. A. M., Koning, J. J., Hira, V. V. V., Nieuwland, R., ... Lok, C. A. R. (2020). Poor perfusion of the microvasculature in peritoneal metastases of ovarian cancer. Clinical and Experimental Metastasis, 37(2). https://doi.org/10.1007/s10585-020-10024-4