The correlation between TAM,MVD, VEGF andMMP-9 expressions among various histological progression, histological grading and staging of breast cancer

Abstract

Breast cancer may progress from an atypical lesion. Angiogenesis has an important role in the
growth, invasion and metastasis of breast cancer, which can be reflected through the microvascular
density (MVD). Tumor associated macrophages (TAMs) are stromal cells that can produce proangiogenic
factor such as vascular endothelial growth factor (VEGF), and induce matrix
metalloproteinase-9 (MMP-9) for degrading extracellular matrix and basement membrane.
Angiogenesis in breast cancer progression and its relationship with histological grading as well
as its staging need to be defined and thus, cancer therapy and prognosis can be determined
more accurately. The aim of this study was to investigate the correlation between TAM, MVD,
VEGF and MMP-9 expressions among fibrocystic lesion, atypical lesion and breast cancer, and
its correlation with histological grading and staging of breast cancer. Using a cross-sectional
study, a total of 50 paraffin embedded tissues of fibrocystic lesion, atypical lesion and breast
cancer were chosen in this study. Those specimens were stained immunohistochemically with
monoclonal antibody (MoAb) anti CD68, von Willebrand factor (vWF), VEGF and MMP-9. The
expressions of VEGF and MMP-9 were counted from the mean numbers of positive tumor cells.
TAMs were counted from numbers of macrophages which expressed CD-68. MVDs were counted
from numbers of microvessels whose endothelial cells expressed vWF, using the Average
Microvessels Count ( AMC) method. The correlation of both markers and different type of breast
lesions were analyzed by using Pearson correlation. There were statistically significant correlations
between TAM (r=0.760; p=0.000), MVD (r=0.659; p=0.000), and MMP-9 (r=0.518; p=0.000),
among several breast lesions and histological grade of breast cancer. The highest of their
expressions was found in the poor grade of cancers. There were statistically significant correlations
between TAM (r=0.581; p=0.000), VEGF (r=0.443; p=0.001) and MVD (r=0.566; p=0.000)
among fibrocystic, atypical lesion and stage II - III of breast cancer. VEGF expression was not
significantly correlated with several histological grade of breast cancer and the highest of its
expression was only found in atypical lesion. This study has suggested that TAM, MVD, VEGF
and MMP-9 expressions might play an important role in the histological progression, histological
grading and staging of breast cancer. The highest expression of VEGF in atypical breast lesion
supported the fact that angiogenic switch already started in the early stage and grade of breast
cancer.