EXPRESSION OF VASCULAR-PERMEABILITY FACTOR (VASCULAR ENDOTHELIAL GROWTH-FACTOR) AND ITS RECEPTORS IN BREAST-CANCER

Solid tumors must induce a vascular stroma to grow beyond a minimal si ze, and the intensity of the angiogenic response has been correlated w ith prognosis in breast cancer patients. Vascular permeability factor (VPF), also known as vascular endothelial growth factor (VEGF), is a s ecreted protein that has been implicated in tumor-associated angiogene sis. 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 mR NA expression in normal breast tissue (13 specimens), comedo-type duct al carcinoma in situ (DCIS) (four specimens), infiltrating ductal carc inoma (12 specimens), infiltrating lobular carcinoma (two specimens), metastatic ductal carcinoma (three specimens) and metastatic lobular c arcinoma (one specimen). Vascular permeability factor mRNA Has express ed 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 d uctal carcinoma, and metastatic ductal carcinoma. In contrast, VPF mRN A was not expressed at high levels in infiltrating lobular carcinoma. We also used in situ hybridization to study the expression of two rece ntly described endothelial cell surface VPI: receptors, flt-1 and kdr. Vascular permeability factor receptor mRNA was strongly expressed in endothelial cells of small vessels adjacent to malignant tumor cells i n 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 inte nse expression of VPF mRNA by breast carcinoma cells and of VPF recept or 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 brea st carcinoma. HUM PATHOL 26:86-91. Copyright (C) 1995 by W.B. Saunders Company