Microvessel density, VEGF expression, and tumor-associated macrophages in breast tumors: correlations with prognostic parameters.

Angiogenesis plays an important role in tumor growth, metastasis, and prognosis. Vascular endothelial growth factor (VEGF) is a potent endothelial mitogen and acts on the angiogenic stimulation of human neoplasias. In infiltrative ductal carcinoma (IDC), VEGF expression is correlated with high vascularity. Tumor-associated macrophages (TAMs) contribute to tumor proliferation, progression and angiogenesis and have a complex role in tumor biology. In this study, the correlations between microvessel density (MVD), VEGF expression, and TAMs and their relations to clinicopathological parameters such as tumor size, metastatic lymph node, mitotic activity index (MAI) and tumor grade were investigated in 48 cases of IDC and 30 infiltrative lobular carcinoma (ILC) cases. MVD showed a significant positive correlation with TAMs, VEGF, metastatic lymph nodes, tumor size and grade in IDC (P < 0.001). In ILC, MVD and tumor size were positively correlated (P = 0.003), while MVD was not correlated with VEGF, TAMs, MAI, metastatic lymph nodes, and grade. These findings are suggestive of angiogenesis stimulation in IDCs by VEGF, driving the macrophages into the tumor area. MVD and TAMs were found to be important prognostic factors in IDCs. On the other hand, however, VEGF did not contribute to angiogenesis in ILCs, and MVD and TAMs did not have any prognostic significance. These results suggest the involvement of factors not related to VEGF in the angiogenesis of lobular carcinoma.

[1]  F Pozza,et al.  Tumor angiogenesis: a new significant and independent prognostic indicator in early-stage breast carcinoma. , 1992, Journal of the National Cancer Institute.

[2]  S. Tsutsui,et al.  Macrophage infiltration and its prognostic implications in breast cancer: the relationship with VEGF expression and microvessel density. , 2005, Oncology reports.

[3]  D. Chhieng,et al.  Microvessel Density and Vascular Endothelial Growth Factor Expression in Infiltrating Lobular Mammary Carcinoma , 2003, The breast journal.

[4]  O. Vinante,et al.  Prognostic significance of vascular endothelial growth factor protein in node-negative breast carcinoma. , 1997, Journal of the National Cancer Institute.

[5]  A. Harris,et al.  Association of macrophage infiltration with angiogenesis and prognosis in invasive breast carcinoma. , 1996, Cancer research.

[6]  Harold E. Dvorak,et al.  Distribution of vascular permeability factor (vascular endothelial growth factor) in tumors: concentration in tumor blood vessels , 1991, The Journal of experimental medicine.

[7]  S Friedman,et al.  Prognostic value of histologic grade nuclear components of Scarff‐Bloom‐Richardson (SBR). An improved score modification based on a multivariate analysis of 1262 invasive ductal breast carcinomas , 1989, Cancer.

[8]  M. Toi,et al.  Quantitative analysis of vascular endothelial growth factor in primary breast cancer , 1996, Cancer.

[9]  S. Ménard,et al.  Prognostic significance of her‐2/neu expression in breast cancer and its relationship to other prognostic factors , 1991, International journal of cancer.

[10]  T. Shono,et al.  Expression of vascular endothelial growth factor and its possible relation with neovascularization in human brain tumors. , 1995, Cancer research.

[11]  L. Happerfield,et al.  Inflammatory infiltrate in invasive lobular and ductal carcinoma of the breast. , 1996, British Journal of Cancer.

[12]  A. Howell,et al.  TUMOUR ANGIOGENESIS AS A PROGNOSTIC MARKER IN INFILTRATING LOBULAR CARCINOMA OF THE BREAST , 1996, The Journal of pathology.

[13]  J. Folkman,et al.  Tumor angiogenesis and metastasis--correlation in invasive breast carcinoma. , 1991, The New England journal of medicine.

[14]  L. Orci,et al.  Vascular endothelial growth factor (VEGF) induces plasminogen activators and plasminogen activator inhibitor-1 in microvascular endothelial cells. , 1991, Biochemical and biophysical research communications.

[15]  Y. Ozeki,et al.  Vascular endothelial growth factor expression in primary esophageal squamous cell carcinoma , 1997, Cancer.

[16]  J. Nyhus,et al.  Vascular endothelial growth factor secretion by tumor-infiltrating macrophages essentially supports tumor angiogenesis, and IgG immune complexes potentiate the process. , 2002, Cancer research.

[17]  E. Manseau,et al.  Increased expression of vascular permeability factor (vascular endothelial growth factor) and its receptors in kidney and bladder carcinomas. , 1993, The American journal of pathology.

[18]  N. Jonjić,et al.  Correlation between vascular endothelial growth factor, angiogenesis, and tumor-associated macrophages in invasive ductal breast carcinoma , 2002, Virchows Archiv.

[19]  J. Monson,et al.  Is the relationship between angiogenesis and metastasis in breast cancer real? , 1992, Surgical oncology.

[20]  D. Ruiter,et al.  Vascular permeability factor expression influences tumor angiogenesis in human melanoma lines xenografted to nude mice. , 1995, The American journal of pathology.

[21]  E. Bauer,et al.  Vascular endothelial growth factor induces interstitial collagenase expression in human endothelial cells , 1992, Journal of cellular physiology.

[22]  W. Dupont,et al.  A retrospective cohort study of histologic risk factors in breast cancer patients , 1982, Cancer.

[23]  H. Joensuu,et al.  Invasive lobular carcinoma of the breast has better short- and long-term survival than invasive ductal carcinoma. , 1997, British Journal of Cancer.

[24]  A. Harris,et al.  Macrophage infiltration is associated with VEGF and EGFR expression in breast cancer , 2000, The Journal of pathology.

[25]  E. Manseau,et al.  Expression of vascular permeability factor (vascular endothelial growth factor) and its receptors in adenocarcinomas of the gastrointestinal tract. , 1993, Cancer research.

[26]  M. Toi,et al.  Tumor angiogenesis is an independent prognostic indicator in primary breast carcinoma , 1993, International journal of cancer.