VEGF and Ki-67 Expression in Colorectal Cancer: The Long-Term Impact on Recurrence and Mortality

Abstract

Objectives: Colorectal cancer is the most frequent and mortal cancer in Portugal. Both angiogenesis and cellular proliferation are core mechanisms to tumoral progression, with VEGF (Vascular Endothelial Growth Factor) and Ki-67, respectively, being widely known markers of those two processes. The purposes of this study are to comprehend VEGF and Ki-67’s impact on colorectal cancer prognosis which include assessing its expression in primary colorectal cancer of patients who underwent surgery, establishing associations between the expression of VEGF and Ki-67 and discovering hypothetical associations between these biomarkers and clinicopathological aspects, relapse, and mortality of patients. Methods: A retrospective study was conducted in our hospital by including 512 patients submitted to surgery, from 2005 to 2010, with a post-operatory diagnosis of colorectal adenocarcinoma. The evaluation of expression of VEGF and Ki-67 in the obtained tissue was made through immunohistochemistry technique. The statistical analysis resourced to association tests and survival analysis. Results: VEGF-A showed association with the variable gender (p-value of 0.016), with its expression being more frequent in men. VEGF-C expression is more common in colon than in rectum (p- value of 0.042). VEGF-C is significantly associated with Ki-67 (p-value of 0.036), with 69.7% of cases where both are positive. All markers are significantly associated with the grade of differentiation, with the VEGF family generally more present in well or moderately differentiated tumours and Ki-67 in the poorly differentiated. While the survival time was generally lower in the presence of any marker or combination, no significant differences were found among the survival analysis. Conclusion: VEGF-A, VEGF-C and Ki-67 expression did not show impact on the prognosis of this sample of patients. There was no significant association with a poorer overall survival or a reduced disease-free survival. Keywords: Colorectal cancer, Ki-67, mortality, recurrence, VEGF