The Relapse of Epithelial Ovarian Cancer Under 2-Year Post-Treatment Observation Based on VEGF-A and VEGFR-2 Expression

Background: Epithelial ovarian cancer is one of the most formidable lethal malignancies, with a 5-year survival rate of approximately 35% for advanced-stage ovarian carcinoma and a 10-year follow-up rate of about 18%. Although several regimens have been evaluated for improvement, relapse remains an inevitable challenge. Recently, specific prognostic factors related to “cell behavior”, including cell proliferation activity such as angiogenesis VEGF (vascular endothelial growth factors) have been recognized. Therefore, this study aims to predict relapse of epithelial ovarian cancer within two years of follow-up based on the expression of vascular endothelial growth factor A (VEGF-A) and vascular endothelial growth factor receptor-2 (VEGFR-2) at the mRNA and protein levels. Methods: This study was conducted at “Dharmais” Cancer Hospital (DCH) with a retrospective cohort design in patients with advanced epithelial ovarian cancer who received complete treatment. The role of angiogenesis factors on relapse in epithelial ovarian cancer in 2 years of observation was evaluated. Semiquantitative expression analysis of VEGF-A and VEGFR-2 (protein) was conducted through the immunohistochemical method using the avidin-biotinperoxidase complex (ABC) method. Meanwhile, the semiquantitative expression of VEGF-A and VEGF-R2 (mRNA level) was carried out using RT-PCR (Reverse Transcription- Polymerase Chain Reaction) - Zyber Green Bioline Kit - method, with specific primers. Results: From 2008 to 2012, only 20 patients were tested for the role of VEGF-A and VEGFR-2 on the incidence of relapse within two years of observation. Among the 20 patients examined for VEGF-A and VEGFR-2 expression, 50% remained disease-free for 20 months, resulting in a cumulative disease-free survival probability of 48.1% for the patient. Those with positive VEGF-A expression at the mRNA level had a shorter median disease-free survival time (18 months), with a lower disease-free survival probability. Patients who showed positive VEGFR-2 expression (at the protein level) had a shorter median disease-free survival time, a lower cumulative probability of disease-free survival (DFS), and a greater risk of relapse (3 times) than patients who did not express (negative) VEGFR-2. In addition, the ROC-based analysis was also performed. Conclusions: Expression of both VEGF-A and VEGFR-2 at mRNA and protein levels can be used as a predictor for relapse of epithelial ovarian cancer. This study showed that a positive VEGF-A expression at the mRNA level is associated with a twofold higher risk of relapse, while positive VEGF-R2 expression at the protein level is associated with a threefold shorter risk of relapse than negative expression.