Clinicopathological Significance of Lymphangiogenesis andTumor Lymphovascular Invasion in Indonesian Breast Cancers

Abstract

<b>Background:</b> Lymphangiogenesis, assessed as lymphovascular density (LVD), is the initial step of generalizedtumor lymphovascular invasion (LVI). It also involves VEGF-C as the most important protein family.Lymphangiogenesis among breast cancer cases correlations with several clinicopathological factors are importantto determine prognosis and treatment strategies, but results have been controversial and require clarification.Aim: To define correlations between VEGF-C expression, LVD and LVI with several clinicopathologicalparameters from Indonesian breast cancer patients. Materials and <br/><b>Methods</b>: Using a cross-sectional study,a total of 48 paraffin-embedded tissues of breast cancer from Dr. Sardjito General Hospital Indonesia wereassessed for VEGF-C expression, LVD and LVI by immunohistochemistry. Correlations of these markers withclinicopathological parameters like patient age, tumor size, lymph node status, grade, ER/PR and Her-2 status,cell proliferation and p-53 expression were investigated by linear analysis. Correlations of VEGF-C expressionand LVI with several clinicopathological parameters were analyzed with Coefficient Contingency Chi-Squaretest. <br/><b>Results</b>: The mean of patients age was 53.0 year, pre and post-menopausal patients accounting for 56.3% and43.8%, respectively. Some 10.4% were well, 41.7% moderate and 47.9% poorly differentiated. ER positivity wasevident in 50% while PR and Her-2 positivity was found in 31.3% and 33.3%, respectively. Breast cancer cellswith over-expression of p-53 was 64.6% and with high cell proliferation was 56.3%. Lymph node metastasis wasnoted in 63.5%, and LVI in 72.9%. Significant correlations were found between LVD and tumor size (p:0.037),grade (p:0.000), lymphnode status (p:0.036), LVI (p:0.003), as well as with p-53 and cell proliferation. Therewere also significant correlation of VEGF-C (p:0.011) and LVI (p:0.001) with tumor grade. Only ER status wasfound to have a correlation with tumor size (p:0.027). <br/><b>Conclusions</b>: This study suggested that in Indonesianbreast cancer patients, lymphangiogenesis is correlated with tumor size, grade, lymph node status and tumorlymphovascular invasion, the latter also being related with p-53 over expression and high cell proliferation.