Explorative investigation of vascular endothelial growth factor receptor expression in primary ovarian cancer and its clinical relevance

• Published in: Gynecologic oncology 2014-06, Vol.133 (3), p.467-472
• Main Authors: Wimberger, Pauline, Chebouti, Issam, Kasimir-Bauer, Sabine, Lachmann, Robert, Kuhlisch, Eberhard, Kimmig, Rainer, Süleyman, Ergün, Kuhlmann, Jan Dominik
• Format: Article
• Language: English
• Subjects: Adenocarcinoma, Mucinous - metabolism; Adenocarcinoma, Mucinous - pathology; Adenocarcinoma, Mucinous - surgery; Adult; Aged; Aged, 80 and over; Angiogenesis; Bevacizumab; Bone Marrow - pathology; Bone Marrow Neoplasms - secondary; Cystadenocarcinoma, Serous - metabolism; Cystadenocarcinoma, Serous - pathology; Cystadenocarcinoma, Serous - surgery; Disseminated tumor cells; Female; Hematology, Oncology and Palliative Medicine; Humans; Immunohistochemistry; Middle Aged; Neoplasm, Residual; Neoplastic Cells, Circulating - pathology; Obstetrics and Gynecology; Ovarian cancer; Ovarian Neoplasms - metabolism; Ovarian Neoplasms - pathology; Ovarian Neoplasms - surgery; Prognosis; Vascular endothelial growth factor receptor; Vascular Endothelial Growth Factor Receptor-1 - metabolism; Vascular Endothelial Growth Factor Receptor-2 - metabolism; Vascular Endothelial Growth Factor Receptor-3 - metabolism; Young Adult
• ISSN: 0090-8258; 1095-6859
• DOI: 10.1016/j.ygyno.2014.03.574

Abstract Objectives The identification of novel molecular biomarkers, predicting outcome of ovarian cancer, is highly desirable. Considering that angiogenesis is a critical factor for ascites development and peritoneal dissemination in ovarian cancer and given that the vascular endothelial growth factor (VEGF) receptor signaling axis is a major driver of angiogenesis, we sought to analyze expression and compartmental distribution of VEGF-receptor family in ovarian cancer and to assess its clinical relevance with regard to established clinicopathological parameters, tumor cell dissemination to the bone marrow (BM) and the patient's survival. Methods A total of 73 patients with primary ovarian cancer were enrolled into this study. Primary tumor tissue was analyzed for the expression of VEGF-R1, VEGF-R2 and VEGF-R3 by immunohistochemistry. The presence of disseminated tumor cells (DTC) in the BM was analyzed by immunocytochemistry using the pancytokeratin antibody A45B/B3 and subsequent automatic detection based on staining and cytomorphology. Results In primary ovarian cancer tissue, VEGF-receptor expression, detected with an overall frequency of 44%, was mostly located in the vascular wall and across the stroma; positivity rates for VEGF-R1, VEGF-R2 and VEGF-R3 were 34%, 18% and 26%, respectively. Total VEGF-receptor expression correlated with residual tumor after primary debulking surgery and the presence of DTC at primary diagnosis (p = 0.035, p = 0.023, respectively). Interestingly, VEGF-R1 positivity significantly correlated with decreased progression-free survival (p = 0.026). Conclusions This is the first report, suggesting total VEGF-receptor status as a molecular biomarker for monitoring tumor cell spread to the BM and, particularly, revealing prognostic significance of VEGF-R1.