Prognostic Value of LYVE-1-Positive Lymphatic Vessel in Tongue Squamous Cell Carcinomas

The density of lymphatic vessels in 52 cases of human tongue squamous cell carcinoma (TSCC) and normal portions was analyzed. TSCC specimens were immunostained with antibodies against lymphatic vessel endothelial hyaluronan receptor 1 (LYVE-1) and podoplanin monoclonal antibody (D2-40). The significance of the LYVE-1-positive vessel density (LVD) was calculated in 6 topographic areas and investigated on the basis of specific clinical and histo- pathological parameters. LYVE-1 positivity was more evident in the muscular area than the submucosal area, while small D2-40-positive lymphatic vessels were not demonstrable in muscular endomysium. The LVD in peri-tumoral submucosal and peri-tumoral muscular areas was lower than in normal counterparts (p<0.01). LVD was higher in the tumor invasion front as compared to tumor-associated stroma (p<0.01). Low LVD in invasion front and peri-tumoral submucosal area was significantly related to regional lymph node metastasis (p<0.05 and p<0.01, respectively). The decrease of LYVE-1-positive lymphatic vessels in the invasion front and peri-tumoral submucosal area would seem to predict cervical lymph node metastasis in TSCC. Lymphatic invasion by tumor cells and tumor metastasis to regional lymph nodes indicate a poor prognosis (1), however, the biological behavior of human lymphatic vessels within tumor lesion is controversial. Lymph node invasion by tumor cells may occur through destruction and penetration into pre- existing or newly generated lymphatic vessels. Another hypothesis is that cancer cells which invade into blood vessels traverse sprouting lymphatic vessels via shunts between blood and sprouting lymphatic vessels (2). These findings indicate that there are certain routes for cancer metastasis to the sentinel lymph node. In oropharyngeal and laryngeal squamous cell carcinoma, there are several previous reports on lymphatic vessel endothelial hyaluronan receptor 1 (LYVE-1)-positive lymphatic vessel distribution and its association with sentinel lymph nodes (3, 4). However, these matters have not yet been investigated in tongue squamous cell carcinoma (TSCC) in conjunction with the consideration of local anatomy, especially with regard to the topographic distribution of lymphatic vessels.