Absence of lymphangiogenesis and intratumoural lymph vessels in human metastatic breast cancer

Early metastasis to lymph nodes is a frequent complication in human breast cancer. However, the extent to which this depends on lymphangiogenesis or on invasion of existing lymph vessels remains controversial. Although proliferating intratumoural lymphatics that promote nodal metastasis have been de...

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Published in:The Journal of pathology Vol. 200; no. 2; pp. 195 - 206
Main Authors: Williams, Cory SM, Leek, Russell D, Robson, Alistair M, Banerji, Suneale, Prevo, Remko, Harris, Adrian L, Jackson, David G
Format: Journal Article
Language:English
Published: Chichester, UK John Wiley & Sons, Ltd 01.06.2003
Wiley
Subjects:
Adult
Aged
Aged, 80 and over
Biological and medical sciences
breast cancer
Breast Neoplasms - blood supply
Breast Neoplasms - metabolism
Breast Neoplasms - pathology
Female
Glycoproteins - metabolism
Gynecology. Andrology. Obstetrics
Humans
Immunoenzyme Techniques
lymphangiogenesis
Lymphatic Metastasis
Lymphatic System - pathology
LYVE-1
Macrophages - pathology
Mammary gland diseases
Medical sciences
metastasis
Middle Aged
Neoplasm Invasiveness
Neoplasm Proteins - metabolism
Neovascularization, Pathologic - pathology
Statistics as Topic
Tumors
VEGF-C
Vesicular Transport Proteins
Human
Immunohistochemistry
Carcinoma
Lymph node
Cytokine
Malignant lymphadenopathy
Lymphatic
breast cancer
VEGF-C
Malignant tumor
Pathology
Mammary gland diseases
Angiogenesis
Vascular endothelium growth factor
metastasis
Tumor progression
lymphangiogenesis
Metastatic
Mammary gland
Molecular biology
Immunofluorescence
LYVE-1
Growth factor
ISSN:0022-3417, 1096-9896
Online Access:Get full text
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Summary:Early metastasis to lymph nodes is a frequent complication in human breast cancer. However, the extent to which this depends on lymphangiogenesis or on invasion of existing lymph vessels remains controversial. Although proliferating intratumoural lymphatics that promote nodal metastasis have been demonstrated in experimental breast tumours overexpressing VEGF‐C, it has yet to be determined whether the same phenomena occur in spontaneous human breast cancers. To address this important issue, the present study investigated the lymphatics in primary human breast carcinoma (75 cases of invasive ductal and lobular breast cancer) by quantitative immunohistochemical staining for the lymphatic endothelial hyaluronan receptor LYVE‐1, the blood vascular marker CD34, and the nuclear proliferation marker pKi67. None of the breast carcinomas was found to contain dividing lymph vessels, even in areas of active haemangiogenesis. Furthermore, the majority of non‐dividing lymph vessels were confined to the tumour periphery where their incidence was low and unrelated to tumour size, grade or nodal status; rather, their density was inversely correlated with tumour aggressiveness as assessed by macrophage density (p = 0.009), and blood microvessel density (p = 0.05, Spearman Rank), as well as with distance from the tumour edge. Finally, a proportion of the peritumoural lymphatics contained tumour emboli associated with hyaluronan, indicating a possible role for LYVE‐1/hyaluronan interactions in lymphatic invasion or metastasis. These results suggest that naturally occurring breast carcinomas invade and destroy lymph vessels rather than promoting their proliferation; that breast tumour lymphangiogenesis may not always occur at physiological VEGF‐C levels; and that nodal metastasis can proceed via pre‐existing lymphatics. Copyright © 2003 John Wiley & Sons, Ltd.
Bibliography:UK Medical Research Council
Association for International Cancer Research - No. 00-311
ark:/67375/WNG-R3RG1CSZ-H
Imperial Cancer Research Fund
ArticleID:PATH1343
istex:871692DCD552D4AE632C8053410B17E98C9397F2
ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:0022-3417
1096-9896
DOI:10.1002/path.1343