Expression profiles of VEGF-A, VEGF-D and VEGFR1 are higher in distant metastases than in matched primary high grade epithelial ovarian cancer

Minna Sopo,Veli-Matti Kosma,Annukka Kivelä,Kirsi Hämäläinen,Hanna Sallinen,Leea Keski-Nisula,Seppo Ylä-Herttuala,Maarit Anttila

doi:10.1186/s12885-019-5757-3

Minna Sopo, Veli-Matti Kosma + Show 6 more

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https://doi.org/10.1186/s12885-019-5757-3

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Abstract

BackgroundIn many malignancies including ovarian cancer, different angiogenic factors have been related to poor prognosis. However, data on their relations to each other or importance as a prognostic factor in ovarian cancer is missing. Therefore, we investigated the expressions of VEGF-A, VEGF-C, and VEGF-D, and the receptors VEGFR1, VEGFR2, and VEGFR3 in patients with malignant epithelial ovarian neoplasms. We further compared expression levels between primary tumors and related distant omental metastases.MethodsThis study included 86 patients with malignant ovarian epithelial tumors and 16 related distant metastases. Angiogenic factor expression was evaluated using immunohistochemistry (n = 102) and qRT-PCR (n = 29).ResultsCompared to primary high grade serous ovarian tumors, the related omental metastases showed higher expressions of VEGF-A (p = 0.022), VEGF-D (p = 0.010), and VEGFR1 (p = 0.046). In univariate survival analysis, low epithelial expression of VEGF-A in primary tumors was associated with poor prognosis (p = 0.024), and short progression-free survival was associated with high VEGF-C (p = 0.034) and low VEGFR3 (p = 0.002). The relative expressions of VEGF-D, VEGFR1, VEGFR2, and VEGFR3 mRNA determined by qRT-PCR analyses were significantly correlated with the immunohistochemically detected levels of these proteins in primary high grade serous ovarian cancer and metastases (p = 0.004, p = 0.009, p = 0.015, and p = 0.018, respectively).ConclusionsThe expressions of VEGF receptors and their ligands significantly differed between malignant ovarian tumors and paired distant metastases. VEGF-A, VEGF-D, and VEGFR1 protein expressions seem to be higher in distant metastases than in the primary high grade serous ovarian cancer lesions.

Highlights

In many malignancies including ovarian cancer, different angiogenic factors have been related to poor prognosis
Immunohistochemical analyses of VEGF-A, VEGF-C, VEGFD, VEGFR1, VEGFR2, and VEGFR3 in primary high grade serous and endometrioid ovarian tumors VEGF-A, VEGF-C, and VEGF-D were mainly detected in the cytoplasm of tumor epithelial cells
VEGF-C staining intensity among epithelial cancer cells was moderate to strong in 89% of primary tumors (IRS, 8), while moderate-to-strong VEGF-A staining intensity was found in 86% of primary tumors (IRS, 6), and VEGF-D staining was at least moderate in 56% of primary tumors (IRS, 4)

Summary

Introduction

In many malignancies including ovarian cancer, different angiogenic factors have been related to poor prognosis. Data on their relations to each other or importance as a prognostic factor in ovarian cancer is missing. We further compared expression levels between primary tumors and related distant omental metastases. At the time of diagnosis, 70% of ovarian cancers are disseminated. Standard treatment strategies include cytoreductive surgery and platinum based chemotherapy. Improved knowledge of cancer growth and dissemination mechanisms at the molecular level has enabled targeted treatments. In ovarian cancer, targeting endothelial cells of the tumor blood vessels is already standard therapy in both recurrent and primary disease [4, 5].

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