Regional difference in intratumoral lymphangiogenesis of oral squamous cell carcinomas evaluated by immunohistochemistry using D2-40 and podoplanin antibody: an analysis in comparison with angiogenesis.
BACKGROUND
Whether tumor cells induce lymphangiogenesis intratumorally or permeate pre-existing lymphatic vessels in the peritumoral area still remains unclear. In this study, we investigated in detail the intratumoral lymphangiogenesis of oral squamous cell carcinomas (SCC) in comparison with tumor angiogenesis.


METHODS
Immunohistochemistry with D2-40, podoplanin antibody, and CD34 antibody were used to evaluate the lymphatic vessel density (LVD) and blood microvessel density (MVD). Vascular endothelial growth factor (VEGF) and VEGF-C expressions of oral SCC were also assessed by immunohistochemistry.


RESULTS
LVD significantly increased in the superficial area of tumor tissue compared with normal mucosa, whereas it decreased in the deep area of intratumoral tissue near the invasion front, in sharp contrast to MVD, which significantly increased throughout tumor tissue. Consistent with the decreased intratumoral LVD and increased intratumoral MVD, VEGF-C expression of tumor cells was down-regulated in the deep area of tumor tissue, while VEGF expression of tumor cells was up-regulated throughout the tumor tissue.


CONCLUSIONS
Lymphangiogenesis in oral SCC varies depending on the region within the tumor tissue. It is not induced in the genuine tumor stroma near the invasion front, probably due to the down-regulation of VEGF-C expression of tumor cells, which is different from VEGF-mediated induction of intratumoral angiogenesis.
Ohno
Fumi
F
The First Department of Oral and Maxillofacial Surgery, School of Dentistry, Aichi-Gakuin University, Nagoya, Japan.
Nakanishi
Hayao
H
Abe
Atsushi
A
Seki
Yasushi
Y
Kinoshita
Atsutaka
A
Hasegawa
Yasuhisa
Y
Tatematsu
Masae
M
Kurita
Kenichi
K
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D018952:Antigens, CD34; D002294:Carcinoma, Squamous Cell / Q000098:blood supply / Q000737:chemistry / Q000473:pathology*; D005260:Female; D006801:Humans; D042583:Lymphangiogenesis / Q000502:physiology*; D042601:Lymphatic Vessels / Q000737:chemistry / Q000473:pathology; D008297:Male; D008562:Membrane Glycoproteins; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000098:blood supply / Q000737:chemistry / Q000473:pathology*; D009363:Neoplasm Proteins / Q000032:analysis*; D009389:Neovascularization, Pathologic / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis*; D042582:Vascular Endothelial Growth Factor C / Q000032:analysis; D000098853:Podoplanin
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D018952:Antigens, CD34; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; D042461:Vascular Endothelial Growth Factor A; D042582:Vascular Endothelial Growth Factor C; C117468:PDPN protein, human; D000098853:Podoplanin; C500987:monoclonal antibody D2-40