Vasculogenic mimicry and pseudo-comedo formation in breast cancer.
Tumors require a blood supply for growth and hematogenous metastases. Until recently, most research in this area has focused on the role of angiogenesis, the recruitment of new vessels into a tumor from preexisting vessels. Previously, in a study of breast cancer (IBC), in which we used established inflammatory breast cancer (IBC) xenografts (WIBC-9) originating from a patient with IBC (Shirakawa et al., Cancer Res 2001:61:445-451), we reported observing vasculogenic mimicry (VM), a condition in which bloodstreams within cancer tissue are not accompanied by a lining of endothelial cells (ECs) (Shirakawa et al., Cancer Res 2002:62:560-566). In the present study, we examined 331 surgically resected breast cancer specimens for evidence of VM, using immunohistochemistry and laser-captured microdissection (LCM) followed by nested reverse transcriptase polymerase chain reaction (RT-PCR). Surprisingly, 7.9% (26 specimens) of the 331 specimens exhibited evidence of VM. Of these 26 VM specimens, 84.6% (22 specimens) exhibited pseudo-comedo formation. RT-PCR analysis of 8 microdissected typical VM specimens revealed expression of Tie-2, Flt-1, thrombin receptor and CD31 in 63, 50, 0 and 0% of specimens, respectively. In contrast, results of RT-PCR analysis of 8 specimens from non-VM tumors were negative for expression of these genes. The 26 VM cases tended to have a higher percentage of hematogenous recurrence (p = 0.059) and a lower percentage of 5-year survival (p = 0.071) than the 305 non-VM cases. However, there were no significant differences in tumor size, lymph node metastasis, estrogen receptors or progesterone receptors between the 2 groups (p > 0.1). Our results suggest that the existence of VM increases the likelihood of hematogenous metastases and is in inverse proportion to prognosis.
Shirakawa
Kazuo
K
Department of Surgery, Omiya Medical Center, Jichi Medical School, Saitama, Japan.
Wakasugi
Hiro
H
Heike
Yuji
Y
Watanabe
Ichiro
I
Yamada
Shigeki
S
Saito
Ken
K
Konishi
Fumio
F
D015703:Antigens, CD / Q000378:metabolism; D001943:Breast Neoplasms / Q000098:blood supply* / Q000473:pathology; D017931:DNA Primers / Q000378:metabolism; D016228:Endothelial Growth Factors / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology*; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D007124:Immunoenzyme Techniques; D008207:Lymphatic Metastasis; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000473:pathology*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism; D042787:Receptor, TIE-2; D018179:Receptors, Thrombin / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D040281:Vascular Endothelial Growth Factor Receptor-1
D015703:Antigens, CD; D017931:DNA Primers; D016228:Endothelial Growth Factors; D016326:Extracellular Matrix Proteins; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D011518:Proto-Oncogene Proteins; D018179:Receptors, Thrombin; C501162:FLT1 protein, human; D020794:Receptor Protein-Tyrosine Kinases; D042787:Receptor, TIE-2; D040281:Vascular Endothelial Growth Factor Receptor-1