Lymphatic vessel density and expressions of lymphangiogenic growth factors in salivary carcinomas.

Nodal metastasis is an important prognostic indicator in head and neck cancers, including salivary carcinomas. In these, the risk for lymph node metastasis is variable and strongly associated with the tumor histologic type. The aim of the current study was to evaluate the lymphatic vessel density (LVD) and expressions of lymphangiogenic growth factors by tumor cells in different histologic types of salivary carcinomas subdivided according to the risk for nodal metastasis. In 15 high-risk (undifferentiated, high-grade mucoepidermoid and salivary duct carcinomas) and 60 low/moderate-risk tumors (adenoid cystic, low/intermediate-grade mucoepidermoid, acinic cell, myoepithelial, epithelial-myoepithelial and polymorphic low-grade carcinomas) the expressions of vascular endothelial growth factor-C (VEGF-C), hepatocyte growth factor (HGF) and D2-40 (for assessing LVD) were examined. No significant differences were encountered between high- and low/moderate/-risk carcinomas regarding LVD and VEGF-C or HGF expressions. Furthermore, the expression of these proteins did not correlate with LVD. Lymphatic vascular invasion was found mainly in high-risk carcinomas. Intratumoral LVD was significantly lower than peritumoral, regardless of the risk for metastasis and primary site of the lesion. The histologic types of salivary carcinomas which are associated with high-risk for nodal metastasis do not present increased LVD or VEGF-C and HGF expressions. The greater tendency for metastasis in these carcinomas seems to be related to their capacity to invade lymph vessels. Further studies on tumor cell interactions with lymphatic endothelial cells are needed to improve our understanding of the metastatic potential of salivary carcinomas.