title: The effect of vascular endothelial growth factor C expression in tumor-associated             macrophages on lymphangiogenesis and lymphatic metastasis in breast cancer.
abstract: The aim of this study was to investigate the effect of vascular endothelial             growth factor-C (VEGF-C) expression in tumor-associated macrophages (TAMs) on             lymphatic microvessel density (LMVD) and lymphatic endothelial cell proliferation             (LECP) and to determine the role of VEGF-C expression in lymphangiogenesis in             patients with breast cancer. Breast cancer tissue specimens confirmed by pathological             analysis were obtained from 75 patients. Samples were observed by microscopy analysis             after immunohistochemical double‑staining. The total number of TAMs and the number             of VEGF-C-positive TAMs were determined. LMVD and LECP were calculated for the             intratumoral and peritumoral areas. Correlation analysis was performed among these             indexes, lymph vessel invasion (LVI) and lymph node metastasis in the peritumoral             regions. Immunohistochemical double-staining demonstrated that VEGF-C was markedly             expressed in TAMs. The number of TAMs, LMVD and LECP in the peritumoral areas             was significantly higher than that in the intratumoral areas (P<0.001). We             observed positive correlations between the following parameters: the number of             TAMs and the peritumoral LMVD (P<0.001), the percentage of TAMs expressing             VEGF-C and the peritumoral LMVD (P<0.001), the number of TAMs and the peritumoral             LECP (P<0.001), and the percentage of TAMs expressing VEGF-C and the peritumoral             LECP (P<0.001). Furthermore, the total number of TAMs and VEGF-C-positive TAMs,             LMVD and LECP in cases with lymph node metastasis or LVI were significantly higher             compared to those in cases without lymph node metastasis or LVI (P<0.01 or             P<0.05). Our findings suggest that TAMs play a critical role in tumor-induced             lymphangiogenesis through upregulating VEGF-C, which may contribute to lymphatic             invasion in breast cancer.
authors.affiliation: Department of Medical Sciences, Jinhua College of Profession and Technology, and Department of Oncology, Jinhua People's Hospital, Jinhua 321007, PR China. mxding@hotmail.com
authors.forename: Mingxing
authors.initials: M
authors.lastname: Ding
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Fu
authors.forename: Haidong
authors.initials: H
authors.lastname: Tan
authors.forename: Ruiquan
authors.initials: R
authors.lastname: Wang
authors.forename: Zhimei
authors.initials: Z
authors.lastname: Chen
authors.forename: Shiping
authors.initials: S
authors.lastname: Ding
mesh_terms: D000328:Adult; D001943:Breast Neoplasms / Q000098:blood supply / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008198:Lymph Nodes / Q000473:pathology; D042583:Lymphangiogenesis; D008207:Lymphatic Metastasis; D042601:Lymphatic Vessels / Q000502:physiology; D008264:Macrophages / Q000378:metabolism* / Q000473:pathology; D008875:Middle Aged; D009367:Neoplasm Staging; D015854:Up-Regulation; D042582:Vascular Endothelial Growth Factor C / Q000378:metabolism*
chemical_list: D042582:Vascular Endothelial Growth Factor C