Tumor lymphangiogenesis in inflammatory breast carcinoma: a histomorphometric study.
OBJECTIVE
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.


METHODS
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.
Van der Auwera
Ilse
I
Translational Cancer Research Group Antwerp, Laboratory of Pathology, University of Antwerp/University Hospital Antwerp, Edegem, Belgium.
Van den Eynden
Gert G
GG
Colpaert
Cecile G
CG
Van Laere
Steven J
SJ
van Dam
Peter
P
Van Marck
Eric A
EA
Dirix
Luc Y
LY
Vermeulen
Peter B
PB
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000096:biosynthesis; D058846:Antibodies, Monoclonal, Murine-Derived; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D002277:Carcinoma / Q000473:pathology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology; D005169:Factor VIII / Q000096:biosynthesis; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006023:Glycoproteins / Q000096:biosynthesis; D018398:Homeodomain Proteins / Q000096:biosynthesis; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation; D008198:Lymph Nodes / Q000473:pathology*; D042583:Lymphangiogenesis; D008207:Lymphatic Metastasis; D008208:Lymphatic System / Q000473:pathology; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D026901:Membrane Transport Proteins; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009389:Neovascularization, Pathologic; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000096:biosynthesis; D011980:Receptors, Progesterone / Q000378:metabolism; D025521:Tumor Suppressor Proteins; D033921:Vesicular Transport Proteins; D000098551:Prospero-Related Homeobox 1 Protein; D000098853:Podoplanin
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D005169:Factor VIII; D006023:Glycoproteins; D018398:Homeodomain Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D011980:Receptors, Progesterone; D025521:Tumor Suppressor Proteins; D033921:Vesicular Transport Proteins; D000098551:Prospero-Related Homeobox 1 Protein; C490441:Pdpn protein, mouse; D000098853:Podoplanin; C119248:LYVE1 protein, human; C117468:PDPN protein, human; C492273:LYVE1 protein, mouse; C500987:monoclonal antibody D2-40