Tumor Lymphangiogenesis in Inflammatory Breast Carcinoma: A Histomorphometric Study

• Published in: Clinical cancer research 2005-11, Vol.11 (21), p.7637-7642
• Main Authors: VAN DER AUWERA, Ilse, VAN DEN EYNDEN, Gert G, COLPAERT, Cecile G, VAN LAERE, Steven J, VAN DAM, Peter, VAN MARCK, Eric A, DIRIX, Luc Y, VERMEULEN, Peter B
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal - biosynthesis; Antibodies, Monoclonal, Murine-Derived; Antineoplastic agents; Biological and medical sciences; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Carcinoma - pathology; Cell Proliferation; Cells, Cultured; D2-40; Endothelium, Vascular - cytology; Factor VIII - biosynthesis; Female; Gene Expression Regulation, Neoplastic; Glycoproteins - biosynthesis; Gynecology. Andrology. Obstetrics; Homeodomain Proteins - biosynthesis; Humans; Immunohistochemistry; Inflammation; inflammatory breast cancer; Lymph Nodes - pathology; Lymphangiogenesis; Lymphatic Metastasis; Lymphatic System - pathology; LYVE-1; Mammary gland diseases; Medical sciences; Membrane Glycoproteins - biosynthesis; Middle Aged; Neoplasm Metastasis; Neovascularization, Pathologic; Pharmacology. Drug treatments; Platelet Endothelial Cell Adhesion Molecule-1 - biosynthesis; Receptors, Progesterone - metabolism; Tumor Suppressor Proteins; Tumors; Vesicular Transport Proteins
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.CCR-05-1142

Purpose: At the time of diagnosis, metastatic dissemination of tumor cells via the lymphatic system has occurred in nearly all patients with inflammatory breast cancer (IBC). The objective of this study was twofold: ( a ) to determine which is the most suitable marker of lymph vessels in primary breast tumors and ( b ) to compare histomorphometric lymph vessel variables in IBC and non-IBC. Experimental Design: Serial sections of 10 IBCs and 10 non-IBCs were immunostained for D2-40, LYVE-1, podoplanin, and PROX-1. Relative lymph vessel area, lymph vessel perimeters, and counts and lymphatic endothelial cell proliferation (LECP) were then measured in D2-40/Ki-67 double-immunostained sections of 10 normal breast tissues, 29 IBCs, and 56 non-IBCs. Results: D2-40 was the most suitable antibody for staining peritumoral and intratumoral lymph vessels. D2-40-stained intratumoral lymph vessels were present in 80% of non-IBCs and 82.8% of IBCs ( P = 0.76). In non-IBC, lymph vessels located in the tumor parenchyma were smaller and less numerous than those at the tumor periphery ( P < 0.0001) whereas in IBC, intratumoral and peritumoral variables were not significantly different. The mean relative tumor area occupied by lymph vessels was larger in IBC than in non-IBC ( P = 0.01). LECP at the tumor periphery was higher in IBC than in non-IBC: median LECP was 5.74% in IBC versus 1.83% in non-IBC ( P = 0.005). Conclusions: The high LECP in IBC suggests that lymphangiogenesis contributes to the extensive lymphatic spread of IBC.