VEGF-C expressing tumor-associated macrophages in lymph node positive breast cancer: impact on lymphangiogenesis and survival.
BACKGROUND
The ability of malignant tumors to metastasize presents a severe challenge in cancer treatment. Lymphatic vessels provide one of the main routes for tumor-metastasis on the way to regional lymph nodes. Increasing evidence suggests that inflammatory cells play an important role in tumor-associated angiogenesis and lymphangiogenesis. Recent data show that a specialized sub fraction of tumor-associated macrophages (TAMs) expressing the lymphoangiogenic growth factors vascular endothelial growth factor-C and -D (VEGF-C/D) at the tumor site, is related to lymphangiogenesis, lymphovascular invasion, and lymph node metastasis. Aim of this study was to clear the role of VEGF-C/D expressing TAMs in invasive breast cancer.


METHODS
One hundred-seven cases of lymph node positive invasive breast cancer were included into the study. Lymphatic microvessel density (LMVD), lymphovascular invasion (LVI), peritumoral inflammatory reaction (PI), and VEGF-C expression in tumors (VEGF-C(T)) and TAMs (VEGF-C(C)) were evaluated by immunohistochemistry and in situ hybridization.


RESULTS
Significant associations were seen between LMVD and LVI, LMVD and VEGF-C(T), and between VEGF-C(T) and VEGF-C(C). Further significant correlations were evaluated between VEGF-C(C)/VEGF-C(T) and PI as well as between PI and LVI. LVI remained an independent prognostic factor for disease-free survival and overall survival.


CONCLUSIONS
Our data provide evidence that the peritumoral inflammatory reaction and VEGF-C expressing TAMs may play an important role in tumor lymphangiogenesis and lymphovascular invasion in invasive breast cancer, implying new potential anti-tumor targets.
Schoppmann
Sebastian F
SF
Department of Surgery, University of Vienna, Austria. sebastian.schoppmann@meduniwien.ac.at
Fenzl
Alexandra
A
Nagy
Katalin
K
Unger
Sandra
S
Bayer
Guenther
G
Geleff
Silvana
S
Gnant
Michael
M
Horvat
Reinhard
R
Jakesz
Raimund
R
Birner
Peter
P
D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000098:blood supply / Q000737:chemistry* / Q000401:mortality / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D042583:Lymphangiogenesis; D008207:Lymphatic Metastasis; D008264:Macrophages / Q000737:chemistry*; D008875:Middle Aged; D042582:Vascular Endothelial Growth Factor C / Q000032:analysis*
D042582:Vascular Endothelial Growth Factor C