The prognostic evaluation of tumor angiogenesis in invasive breast carcinoma

Abstract

Microvessel density (MVD) was analyzed for associations with clinical and pathological factors as well as with other potential known prognostic factors such as: steroid receptor content (ER, PgR), p53 and proliferation associated indices (Ki-67, PCNA). In the present study microvascular quantification was undertaken on 145 cases of breast carcinoma after immunohistochemical staining of tumor vessel, using polyclonal antibody to factor VIII related antigen. Microvessel quantification was performed at x400 magnification in the three most vascular areas of the tumors (hot spots) usually located at the periphery or growing front of the tumor. In addition, a semi-quantitative evaluation of the number of vessels per mm2 of highest intratumoral microvessel density (MVD) was performed by use of an image analysis system. Significant correlation was observed in MVD by computerized analysis and by light microscopy counting (p=0.02). Survival analysis showed increased mortality risk associated with low MVD estimated by both methods (p-0.043 and p=0.041 respectively) including node-negative and node positive subsets.). In addition low MVD was correlated with recurrence (p=0.02) and metastatic disease (p=0.0016) in the cases estimated by light microscopy. However in multivariant analysis, MVD was independently correlated with relapse-free and over patients survival. MVD was higher in lobular than in ductal cell carcinoma (p=0.015). MVD was positive correlated with estrogen receptor status (p=0.04) and inversely with tumor size (p=0.004). No association was found with tumor grade and lymph node status The results of the present study show that the MVD (determined at a microscopic level or by image analysis) correlated with better prognostic parameter maybe due to better responded to treatment. Furthermore, MVD in addition to breast cancer heterogeneity, could be reflects different phases of tumor growth.