Correlation of the expression of the receptor of vascular endothelial growth factor (VEGF) and KI-67 with pathological variables in breast cancer patients

Abstract

Correlation of the expression of the receptor of vascular endothelial growth factor (VEGF) and KI-67 with pathological variables in breast cancer patients. Background: Many studies have been conducted on proteins that have action on cell proliferation, such as VEGF and KI-67. VEGF acts in the angiogenesis required for tumor growth. The KI-67 correlates with proliferation of tumor cells, probably reflecting its aggressiveness. Objective: To analyze the correlation of VEGFR1 and KI-67 with pathological variables. Methods: The study was approved by the Committee on Ethics in research, University Hospital of Porto Alegre (RS). Between March 2008 and April 2009 we included 41 patients with early breast cancer (T1 and T2). We used H&E staining for tumor analysis, histological grade and vascular invasion, and immunohistochemistry evaluation with antibodies specific for VEGF receptors, KI-67, p53, estrogen receptor (ER), using quality score until 3+ of the evaluation of intensity of stain and quantitative until 5+, to evaluate the expression percentage of stained cells. The total score, add either, can reach 8+ Only the KI-67 was categorized by percentage of stained cells in the IHC and considered positive above 20%. Statistics: correlation and pearson’s chi square and, for the significant variables, used the multivariate analysis. Results: The receptor VEGFR1 in both color intensity score and the total score, correlated positively with T1 tumors (p=.01), with the estrogen receptor positive (p=.01) and negative expression of KI-67 (p=.02). The expression of KI-67 correlates positively with p53 (p=.00) and with estrogen receptor negative (p=.04) and weak correlation with vascular invasion (p=.09) and histological grade undifferentiated (p=.07). Discussion: evaluation of tumor markers that may respond to targeted therapy is a goal to be pursued. The positive correlation of VEGF with the status of ER has been reported and is consistent with our results. The expression of KI-67 is associated with poor outcome. The controversial results of the markers reflect the difficulty in standardizing evaluations (used reagents, procedures and score) and prevent its prognostic validation. Conclusions: The clinical correlation between the results obtained and outcomes of disease-free survival and overall survival could not be measured. However, the data presented can enhance the studies done and seek better methods for standardization of future results and statistical analysis.