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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

  • Original Article – Clinical Oncology
  • Published:
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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.

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Authors and Affiliations

Authors

Contributions

This study was designed by Jalid Sehouli and Elena Braicu. The clinical data were collected by Sven Mahner, Linn Woelber, Katharina Prieske, Nicole Concin, Ignace Vergote, Els Van Nieuwenhuysen, Patriciu Achimas-Cadariu, Joanna Glajzer, Hannah Woopen, Mandy Stanske, Hagen Kulbe, Silvia Darb-Esfahani and Carsten Denkert. The immunohistochemistry staining was evaluated by Jun Guan, Eliane Taube and Silvia Darb-Esfahani. The results were analyzed by Jun Guan and Rolf Richter. The tables and figures were drawn by Jun Guan. And Jun Guan summarized all the findings and wrote the manuscript. Elena Braicu, Ilary Ruscito, Rolf Richter, Hagen Kulbe, Sven Mahner, Linn Woelber and Katharina Prieske revised the article.

Corresponding author

Correspondence to Elena Ioana Braicu.

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Conflict of interest

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.

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Guan, J., Darb-Esfahani, S., Richter, R. et al. 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. J Cancer Res Clin Oncol 145, 1063–1073 (2019). https://doi.org/10.1007/s00432-019-02877-4

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