Impact of vascular endothelial growth factor (VEGF) and hypoxia-inductible factor-1 alpha (HIF-1) expression on the prognosis of locally advanced cervical carcinoma (LACC) treated with radiochemotherapy.

Abstract

e17023 Background: Combination of radiotherapy plus platinum-based chemotherapy (RT-CT) is considered the standard treatment in LACC. The risk of recurrence after local treatment is around 50-70%. The role of angiogenesis in tumor progression has been shown in large series. The aim of this study was to determinate the impact of the expression of VEGF and HIF-1 on disease-free survival (DFS) and overall survival (OS) in patients with LACC receiving RT-CT. Methods: Expression of VEGF and HIF–1 was assessed by an immunohistochemistry (IHC) assay in 115 cases. Inmunostainning was considered negative (< 10% of cells), slightly positive (< 25%), moderate (26%-50%) and strongly positive (> 50%). A univariate analysis was carried out for each variable using the log-rank test. Subsequently, a multivariate analysis was performed employing Cox’s proportional hazards model. Results: 115 patients (p) with LACC were included and received RT-CT between January/2003 and December/2012. IHC revealed absence of expression of VEGF in 12 (10,4%) cases, slightly positive in 34 (29,6%), moderate in 30 (26,1%) and strongly positive in 39 (33,9%). The expression of HIF-1 was negative in 63 (54,8%) cases and positive (weak or moderate) in 52 (45,2%). 76p (66,1%) showed a complete clinical response (CR), 26p (22,6%) partial response and 13p (11,3%) stable disease or progression. The median follow–up was 35 months (1-140). 56p (48,7%) relapsed. Univariate analysis indicate that ECOG > 1, tumor size ≥ 4,5 cm, FIGO stage III-IVA, lymph nodes positive, non CR, CA125 post-treatment ≥ 35 U/mL, hemoglobin levels <11 mg/dl (basal, nadir and post-treatment), strong expression VEGF and positive expression of HIF – 1 were all associated with a significant lower OS and DFS. In multivariate analysis strong expression of VEGF remained statistically significant, as tumor size, non CR and hemoglobin level post-treatment < 11g/dL. Conclusions: IHC-assessed strong expression of VEGF was independent prognostic factor of shorter OS and DFS in patients with LACC treated with RT-CT. IHC determination of VEGF could be useful in clinical practice.