Lymphatic Vessel Density and Lymphangiogenesis in Human Oral Squamous Cell Carcinoma

Abstract

Lymphatic vessels are distributed directly under the epithelium of the oral mucosal. In the present study, we investigated whether lymphoangiogenseis in tumors occurs in human oral squamous cell carcinoma and whether the density of tumor lympahngiogensis may be related to the risk of lymph node metastasis. Moreover, these analyses identified peritumoral lymphatic vascular density as a novel prognostic indicator for the risk of lymph node metastasis in oral squamous cell carcinoma. LYVE-1, which was an endothelial cell hyaluronic acid receptor, has been identified as a peculiar protein of endothelial cells of lymphatic vessels. LYVE-1 expression in the carcinoma tissue was divided into two types. In one it appears in contact with the cancer nest. This shows contact with basal-like cells which are located on the outer side of the cancer nest, and observation via light microscope is unable to show intervention of the fibrous connective tissues. The other case is that in which there is intervention of the clear fibrous connective tissues between the cancer nest and LYVE-1-positive cells. The cancer cells showed a high degree of differentiation, increased by the formation of the cancer nest, and in what is called highly-differentiated squamous cell carcinoma whose invasion pattern showed INF alpha, the cells staining positive to the LYVE-1 antibody could be recognized only negligibly in the connective tissue. Positive staining of the LYVE-1 antibody was seen in the endothelial cells presenting in the lumen formed between each small cancer nest in the case of undifferentiated squamous cell carcinoma in which the cancer nest was very small and composed of undifferentiated cancer cells. In this case the cancer invasion pattern shows INFy. In addition, the expression of LYVE-1 was recognized in cells which had not formed into the lumen between the cancer nests. In the meantime, VEGF-C was expressed in endothelial cells which formed the lumen and cancer cells. In the cancer cells which formed the large cancer nest, the expression of VEGF-C was recognized in basal-like cells which located at the periphery of the nest. VEGF-C was expressed in the cancer cells which formed the small nest. The results of this study show that the incidence of VEGF-C expression in the cancer cell is low. However, lymphatic vessels form in carcinoma tissue at a high rate when VEGF-C is expressed. It was shown that in this study, the close proximity of the lymphatic vessel to the cancer nest shows correlation to lymph node metastasis. This should affect the determination of the operation range, and have a direct influence on prognosis. It is also indicated that LYVE-1 can act as a useful marker in oral cancer.