TY - JOUR
T1 - Poor perfusion of the microvasculature in peritoneal metastases of ovarian cancer
AU - Kastelein, Arnoud W.
AU - Vos, Laura M.C.
AU - van Baal, Juliette O.A.M.
AU - Koning, Jasper J.
AU - Hira, Vashendriya V.V.
AU - Nieuwland, Rienk
AU - van Driel, Willemien J.
AU - Uz, Zühre
AU - van Gulik, Thomas M.
AU - van Rheenen, Jacco
AU - Ince, Can
AU - Roovers, Jan Paul W.R.
AU - van Noorden, Cornelis J.F.
AU - Lok, Christianne A.R.
N1 - Funding Information: The authors thank Yasin Ince for technical support and assistance in graphic design, and Robert Evers for his assistance in sample preparation, staining and sectioning. We would also like to acknowledge the NKI-AVL Core Facility Molecular Pathology & Biobanking (CFMPB) for supplying NKI-AVL lab support. Publisher Copyright: © 2020, The Author(s). Copyright: Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/4/1
Y1 - 2020/4/1
N2 - 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.
AB - 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.
KW - EOC
KW - Incident dark field imaging
KW - Microcirculation
KW - Microvasculature
KW - Peritoneal carcinomatosa
UR - http://www.scopus.com/inward/record.url?scp=85079121461&partnerID=8YFLogxK
U2 - https://doi.org/10.1007/s10585-020-10024-4
DO - https://doi.org/10.1007/s10585-020-10024-4
M3 - Article
C2 - 32008138
SN - 0262-0898
VL - 37
SP - 293
EP - 304
JO - Clinical and Experimental Metastasis
JF - Clinical and Experimental Metastasis
IS - 2
ER -