Abstract

Solid tumors must induce a vascular stroma to grow beyond a minimal size, and the intensity of the angiogenic response has been correlated with prognosis in breast cancer patients. Vascular permeability factor (VPF), also known as vascular endothelial growth factor (VEGF), is a secreted protein that has been implicated in tumor-associated angiogenesis. Vascular permeability factor directly stimulates endothelial cell growth and also increases microvascular permeability, leading to the extravasation of plasma proteins, which alter the extracellular matrix in a manner that promotes angiogenesis. To determine whether VPF has a role in breast cancer, we used in situ hybridization to study VPF mRNA expression in normal breast tissue (13 specimens), comedo-type ductal carcinoma in situ (DCIS) (four specimens), infiltrating ductal carcinoma (12 specimens), infiltrating lobular carcinoma (two specimens), metastatic ductal carcinoma (three specimens) and metastatic lobular carcinoma (one specimen). Vascular permeability factor mRNA was expressed at a low level by normal duct epithelium but was expressed at high levels in tumor cells in all cases of comedo-type DCIS, infiltrating ductal carcinoma, and metastatic ductal carcinoma. In contrast, VPF mRNA was not expressed at high levels in infiltrating lobular carcinoma. We also used in situ hybridization to study the expression of two recently described endothelial cell surface VPF receptors, flt-1 and kdr. Vascular permeability factor receptor mRNA was strongly expressed in endothelial cells of small vessels adjacent to malignant tumor cells in DCIS, infiltrating ductal carcinoma, and metastatic ductal carcinoma. In contrast, no definite labeling for receptor mRNA was detected in infiltrating lobular carcinoma or nonmalignant breast tissue. The intense expression of VPF mRNA by breast carcinoma cells and of VPF receptor mRNA by endothelial cells of adjacent small blood vessels provides strong evidence linking VPF expression to the angiogenesis associated with comedo-type DCIS, infiltrating ductal, and metastatic ductal breast carcinoma.

Keywords

Vascular endothelial growth factorDuctal carcinomaPathologyAngiogenesisVascular permeabilityLobular carcinomaBiologyBreast carcinomaCarcinoma in situExtravasationCancer researchComedoCarcinomaBreast cancerMedicineCancerInternal medicine

MeSH Terms

Breast NeoplasmsCarcinomaCarcinoma in SituCarcinomaDuctalBreastEndothelial Growth FactorsFemaleHumansIn Situ HybridizationLymphokinesRNAMessengerReceptor Protein-Tyrosine KinasesReceptorsGrowth FactorReceptorsVascular Endothelial Growth FactorVascular Endothelial Growth Factor AVascular Endothelial Growth Factors

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Publication Info

Year
1995
Type
article
Volume
26
Issue
1
Pages
86-91
Citations
619
Access
Closed

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Cite This

Lawrence F. Brown, Brygida Berse, Robert W. Jackman et al. (1995). Expression of vascular permeability factor (vascular endothelial growth factor) and its receptors in breast cancer. Human Pathology , 26 (1) , 86-91. https://doi.org/10.1016/0046-8177(95)90119-1

Identifiers

DOI
10.1016/0046-8177(95)90119-1
PMID
7821921

Data Quality

Data completeness: 81%