Tumor Angiogenesis and the Relationship to the Prognosis in Breast Cancer

Shin, Yong Sheop; Lee, Min Hyo; Joo, Jeong Il; Ju, Young Tae; Jeong, Chi Young; Park, Soon Tae; Ha, Woo Song; Choi, Sang Kyung; Hong, Soon Chan; Kwon, Soo In; Lee, Young Joon

Abstract

BACKGROUND: The status of axillary lymph nodes has been the most important prognostic factor in operable breast carcinomas, but it does not fully account for the varied disease outcome. More accurate prognostic indicators would help in the selection of patients at high risk for disease recurrence and death and in the selection of candidates for systemic adjuvant therapy. Many studies have suggested that tumor growth is angiogenesis-dependent and that implies an increase in the delivery of nutrients to the tumor cells. This neovascularization also increases the opportunity for tumor cells to enter the circulation, which indicates the importance of tumor angiogenesis to the metastastic potential of tumors. The aim of this study was designed to further define the relationship of microvessel density (MVD) to overall and relapse- free survival and to other reported prognostic indicators in breast carcinomas.
METHODS
To investigate the status of angiogenesis in breast carcinomas, we highlighted the microvessels within primary invasive breast carcinomas by using a immunohistochemical study with a monoclonal antibody against the factor-VIII-related antigen. Using light microscopy, we counted the microvessels per 200x field in the most active areas of neovascularization, and we graded the microvessel density.
RESULTS
In this study 86 patients with a breast carcinoma were classified into two groups. There were 47 patients with low MVD (<42/200xPF) and 39 patients with high MVD (> or =42/200xPF). The MVD was in the range between 8 and 173. A significant correlations between microvessel density and the overall survival rates (p=0.0003) and relapse-free survival rates (p=0.0003) were found in all patients. Also, there was a significant association of tumor size and lymph node metastasis states with the overall survival rates and the relapse-free survival rates in all patients. A significant correlation was found between MVD and tumor size (p=0.010). The relapse-free 5-years survival rate of low-MVD patients was 85.5+/-5.52%, and that of high-MVD patients was 44.36+/-9.73% (p=0.0003). The overall 5-yearssurvival rate of low-MVD patients was 84.12+/-6.01%, and that of high-MVD patients was 37.75+/-10.07% (p=0.0003).
CONCLUSIONS
In conclusion the present study found a significant correlation between MVD and both tumor size, lymph-node metastasis. The present study shows that the MVD in the area of the most intense neovascularization in an invasive breast carcinoma is an independent and significant prognostic indicator for the overall survival rate and the relapse-free survival rate in patients. Thus, determination of the MVD in an invasive breast carcinoma would be valuable.