The effect of the peritoneal tumor microenvironment on invasion of peritoneal metastases of high-grade serous ovarian ca
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ORIGINAL ARTICLE
The effect of the peritoneal tumor microenvironment on invasion of peritoneal metastases of high-grade serous ovarian cancer and the impact of NEOADJUVANT chemotherapy J. O. A. M. van Baal 1 & C. A. R. Lok 1 & E. S. Jordanova 1 & H. Horlings 2 & W. J. van Driel 1 & F. C. Amant 1 & K. K. Van de Vijver 2,3 Received: 27 September 2019 / Revised: 19 February 2020 / Accepted: 8 March 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract Peritoneal metastases of high-grade serous ovarian cancer (HGSOC) are small-sized deposits with superficial growth toward the peritoneal cavity. It is unknown whether integrity of the peritoneal elastic lamina (PEL) correlates with the peritoneal tumor microenvironment (pTME) and whether neoadjuvant chemotherapy (NACT) affects the pTME. We explored integrity of PEL, composition of pTME, effects of NACT, and the prognostic implications in patients with extensive peritoneal metastases of HGSOC. Peritoneal samples (n = 69) were collected during cytoreductive surgery between 2003 and 2016. Clinical data were collected from medical charts. Integrity of PEL was evaluated with elastic stains. T cell (CD3, CD8) and M2-macrophage markers (CD163) were scored using algorithms created in definiens tissue studio. Patients with a disrupted PEL (n = 39; 57%), more often had residual disease after surgery (p = 0.050), compared to intact PEL. An intact PEL was associated with increased intraepithelial (ie) CD8+ cells (p = 0.032), but was not correlated with improved survival. After NACT, increased ieCD3+ cells were shown, compared to no-NACT (p = 0.044). Abundance of total CD3+ and CD8+ cells were associated with PFS (multivariate HR 0.40; 95%CI 0.23–0.69 and HR 0.49; 95%CI 0.29–0.83) and OS (HR 0.33; 95%CI 0.18–0.62 and HR 0.36; 95%CI 0.20–0.64). M2-macrophage infiltration was not correlated with survival. NACT increases abundance of ieCD3+ cells in peritoneal metastases of HGSOC. Increase of CD3+ and CD8+ cells is associated with improved PFS and OS. This suggests that CD3+ and CD8+ cells may function as prognostic biomarkers. Their role as predictive biomarker for chemotherapy or immunotherapy response in HGSOC warrants further research. Keywords Peritoneal elastic lamina . Peritoneal tumor microenvironment . Peritoneal metastases . High-grade serous ovarian cancer . Tumor-infiltrating lymphocytes
Introduction Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00428-020-02795-8) contains supplementary material, which is available to authorized users. * J. O. A. M. van Baal [email protected] 1
Department of Gynecology, Center for Gynecologic Oncology Amsterdam, P.O. Box 90203, Amsterdam 1006, BE, The Netherlands
2
Division of Diagnostic Oncology & Molecular Pathology, The Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands
3
Department of Pathology, Ghent University Hospital, Cancer Research Institute Ghent (CRIG), Ghent, Belgium
Epithelial ovarian cancer (EOC) is the leading c
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