Lymphatic Vessels and High Endothelial Venules are Increased in the Sentinel Lymph Nodes of Patients with Oral Squamous Cell Carcinoma Before the Arrival of Tumor Cells

To investigate the change of vasculature in the sentinel lymph node (SLN) of patients with oral squamous cell carcinoma. Immunohistochemical staining of SLNs in 58 patients was performed with two monoclonal antibodies (MAb): anti-D2-40 MAb for lymphatic endothelial cells, and anti-MECA-79 MAb for high endothelial venules (HEV). Twelve metastatically involved (m(+)) SLNs, 120 uninvolved (m(-)) SLNs, and 35 non-SLNs (control) were available for analyses. Vessel densities were measured by computer-assisted analyses in the entire region of SLN. Correlations were assessed between vessel density and clinicopathologic variables, including vascular endothelial growth factor C of primary tumor. Lymphatic vessel density (LVD) in SLNs was higher than that in control LNs [2361.8 mu m(2)/high-power field (HPF) (624.3-4758.5) vs. 1621.9 mu m(2)/HPF (465.3-3453.5), P = 0.005]. LVD of m(-) SLNs [2662.4 mu m(2)/HPF (624.3-4758.5)] and m(+/-) SLNs [4946.6 mu m(2)/HPF (2009.3-8698.8)] were both statistically significantly higher compared to control. HEV densities in m(-) SLNs [14029.7 mu m(2)/HPF (10465.7-17927.1)] as well as m(+/-) SLNs [18258.5 mu m(2)/HPF (8408.9-27706.0)] were also significantly higher than those in control [10350.5 mu m(2)/HPF (7807.8-12541.1)]. By multivariate analysis, the degree of vascular endothelial growth factor C expression of primary tumor showed significant correlation with LVD of SLNs (odds ratio 9.46, 95% confidence interval 1.73-51.5, P = 0.009), which was not the case in HEV. Lymphatic vessels and HEVs were increased in SLNs, regardless of metastatic status of SLNs. Vascular endothelial growth factor C expression of primary tumor may contribute to the premetastatic change within SLNs of oral squamous cell carcinoma.