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. 2019 Apr;145(4):1063-1073.
doi: 10.1007/s00432-019-02877-4. Epub 2019 Feb 27.

Vascular endothelial growth factor receptor 2 (VEGFR2) correlates with long-term survival in patients with advanced high-grade serous ovarian cancer (HGSOC): a study from the Tumor Bank Ovarian Cancer (TOC) Consortium

Jun Guan  1   2 , Silvia Darb-Esfahani  2   3 , Rolf Richter  1   2 , Eliane T Taube  2   3 , Ilary Ruscito  1   2   4 , Sven Mahner  2   5   6 , Linn Woelber  2   5 , Katharina Prieske  2   5 , Nicole Concin  2   7 , Ignace Vergote  2   8 , Els Van Nieuwenhuysen  2   8 , Patriciu Achimas-Cadariu  2   9 , Joanna Glajzer  1   2 , Hannah Woopen  1   2 , Mandy Stanske  1 , Hagen Kulbe  1   2 , Carsten Denkert  1   2 , Jalid Sehouli  1   2 , Elena Ioana Braicu  10   11
Affiliations

Vascular endothelial growth factor receptor 2 (VEGFR2) correlates with long-term survival in patients with advanced high-grade serous ovarian cancer (HGSOC): a study from the Tumor Bank Ovarian Cancer (TOC) Consortium

Jun Guan et al. J Cancer Res Clin Oncol. 2019 Apr.

Abstract

Objective: The impact of angiogenesis on long-term survival of high-grade serous ovarian cancer (HGSOC) patients remains unclear. This study investigated whether angiogenic markers correlated with 5-year progression-free survival (PFS) in a large cohort of matched advanced HGSOC tissue samples.

Methods: Tumor samples from 124 primary HGSOC patients were retrospectively collected within the Tumor Bank Ovarian Cancer ( http://www.toc-network.de ). All patients were in advanced stages (FIGO stage III-IV). No patient had received anti-angiogenesis therapy. The cohort contains 62 long-term survivors and 62 controls matched by age and post-surgical tumor residuals. Long-term survivors were defined as patients with no relapse within 5 years after the end of first-line chemotherapy. Controls were patients who suffered from first relapse within 6-36 months after primary treatment. Samples were assessed for immunohistochemical expression of vascular endothelial growth factor (VEGF) A and VEGF receptor 2 (VEGFR2). Expression profiles of VEGFA and VEGFR2 were compared between the two groups.

Results: Significant correlation between VEGFA and VEGFR2 expression was observed (p < 0.0001, Spearman coefficient 0.347). A high expression of VEGFR2 (VEGFR2high) was found more frequently in long-term survivors (77.4%, 48/62) than in controls (51.6%, 30/62, p = 0.001), independent of FIGO stage and VEGFA expression in multivariate analysis (p = 0.005). Also, VEGFR2high was found the most frequently in women with PFS ≥ 10 years (p = 0.001) among all 124 patients. However, no significant association was detected between VEGFA expression and 5-year PFS (p = 0.075).

Conclusions: VEGFR2 overexpression significantly correlated with long-term PFS in HGSOC patients, independent of age, FIGO stage, tumor residual and VEGFA expression.

Keywords: Advanced primary HGSOC; Angiogenesis; Long-term survival; Ovarian cancer; VEGFA; VEGFR2.

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Conflict of interest statement

Dr. Elena Ioana reports grants, personal fees and other from Roche Pharma, personal fees from Clovis, personal fees and other from TesaroBio, personal fees and other from AstraZeneca, personal fees from Amgen, personal fees from Incyte, grants from Molecular Health, outside the submitted work; Dr. Sven Mahner reports research support, advisory board, honoraria and travel expenses from AstraZeneca, Bayer, Boehringer Ingelheim, Clovis, Eisai, GlaxoSmithKline, Jenapharm, Janssen-Cilag, Medac, MSD, Novartis, PharmaMar, Roche, Sensor Kinesis, Teva, Tesaro; Dr. Linn Woelber reports grants from medac oncology, during the conduct of the study; grants, personal fees and non-financial support from medac oncology, personal fees and non-financial support from Tesaro, personal fees from Roche, Pharmamar, Tewa, Astra Zeneca, Jenapharm and Janssen-Cilag, outside the submitted work; Dr. Carsten Denkert is the cofounder and shareholder of Sividon Diagnostics and in advisory board of Teva, Roche, AstraZeneca, Celgene, Pfizer, Novartis, Daiichi, and MSD. Other authors have no conflict of interest.

Figures

Fig. 1
Fig. 1
Age, tumor residual and FIGO stage of patients in long-term and control groups
Fig. 2
Fig. 2
VEGFA and VEGFR2 expression by immunohistochemistry: weak expressions of VEGFA (a) and VEGFR2 (e) in tumor cells; strong expressions of VEGFA (b) and VEGFR2 (f) in tumor cells with weak background staining in stroma cells; and IRS distribution of VEGFA (c, d) and VEGFR2 (g, h) expression in long-term and control groups
Fig. 3
Fig. 3
Difference in VEGFA and VEGFR2 expressions between long-term and the control groups: VEGFA (a) and VEGFR2 (b) expression and their co-expression (c) between two groups in all patients (n = 124); difference in VEGFA (d) and VEGFR2 (e) expressions between two groups in no-residual patients (n = 96); and difference in VEGFA (f) and VEGFR2 (g) expressions between two groups in with-residual patients (n = 28)
Fig. 4
Fig. 4
Correlation between VEGFA/VEGFR2 expressions and PFS: IRS of VEGFA (a) and VEGFR2 (b), and high expression of VEGFA (c) and VEGFR2 (d) in patients with subgroups according to PFS duration
See this image and copyright information in PMC

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