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[Cancer Research 61, 445-451, January 15, 2001]
© 2001 American Association for Cancer Research

Advances in Brief

Absence of Endothelial Cells, Central Necrosis, and Fibrosis Are Associated with Aggressive Inflammatory Breast Cancer1

Kazuo Shirakawa, Hitoshi Tsuda, Yuji Heike, Kazunori Kato, Rumiko Asada, Motoko Inomata, Hiroki Sasaki, Fujio Kasumi, Masataka Yoshimoto, Toshihiko Iwanaga, Fumio Konishi, Masaaki Terada and Hiro Wakasugi2

Pharmacology Division [K. S., K. K., R. A., M. I., H. W.], Pathology Division [H. T.], and Genetics Division [H. S., M. T.], National Cancer Center Research Institute, Tokyo 104-0045; Department of Clinical Oncology and Clinical Research, National Shikoku Cancer Center, Ehime, 790-0007 [Y. H.]; Department of Surgery, Japanese Foundation for Cancer Research, Tokyo 170-8455 [F. Ka., M. Y.]; Department of Veterinary Anatomy, Hokkaido University, Sapporo 060-8638 [T. I.]; and Department of Surgery, Omiya Medical Center, Jichi Medical School, Omiya 330-0834 [K. S., F. Ko.], Japan

We recently established a new human inflammatory breast cancer (IBC) xenograft (WIBC-9) originating from a patient with IBC. The graft was transplantable in BALB/c nude and severe combined immunodeficient (SCID) mice. WIBC-9 was frequently accompanied by lung metastasis and exhibited erythema of the overlying skin, reflecting its human counterpart. Histological study of the original tumor and WIBC-9 revealed invasive ductal carcinoma with a hypervascular structure of solid nests and marked lymphatic permeation in the overlying dermis. In the central part of the solid nests, absence of endothelial cells, central necrosis, and fibrosis were observed. In vitro, WIBC-9 formed tube-like structures and loops, reflecting its in vivo feature and its human counterpart. WIBC-9 exhibited aneuploidy, ErbB-2 gene amplification, and an absence of estrogen receptor and progesterone receptor, which is consistent with IBC. Comparative studies of WIBC-9, three established non-IBC xenografts, and a human breast cancer cell line (SK-BR3) by reverse transcription-PCR, ELISA, and immunohistochemistry indicated that certain human genes (interleukin 8, vascular epidermal growth factor, basic fibroblast growth factor, angiopoietin 13, Flt-1, Tie-2, and Tie-1) and certain murine genes (integrin {alpha}vß3, flt-1, tie-2, vascular epidermal growth factor, and CD31) were overexpressed in exposure to tumor cells. The molecular basis and these unique histological features may be associated with aggressive IBC on angiogenic and nonangiogenic pathways.




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