Expression Of VEGF-C, VEGFR-3 And Nm23-H1 In Oral Squamous Cell Carcinoma Correlates With Lymphatic Metastases

Backgroud:Most oral cancer (above 90%) is oral squamous cell carcinoma;many patients with oral cancer are detected late, with regional lymph node metastases. Malignant tumor metastasizes by different mechanisms comprising direct invasion of the surrounding tissue and spreading via the lymphatic or vascular system. Metastasis is a frequent and lethal complication of cancer, including multiple gene and poly-procedure. On the one hand , Lymphangiogenesis and angiogenesis are essential to tumor metastasis, on the other hand, inactivation of non-metastasis gene also plays an important role. Vascular endothelial growth factor-C (VEGF-C) is a recently described special lymphangiogenic factor. Increased expression of VEGFR-3 ligand VEGF-C in primary tumours correlates with dissemination of tumour cells to regional lymph nodes. The nm23 gene is a putative tumour and metastasis suppressor gene with two subgroups, nm23-H1 and nm23-H2. A number of studies have found that reduction of nm23-H1 expression is associated with increased metastatic potential in several human malignancies. However, to our knowledge, there are rare report about the expression of VEGF-C, VEGFR-3 and nm23-H1 in oral carcinoma correlates with lymphangiogenesis and lymphatic metastases.Aims:To explore the role of VEGF-C, VEGFR-3 and nm23-Hl in the process of lymphangiogenesis and lymphatic metastasis in oral squamous cell carcinoma. Experiment content: first, the expression of VEGF-C ^ VEGFR-3 and nm23-Hl in oral squamous cell carcinoma, precancerous change and benign lesion;second, the correlation between VEGF-C, nm23-Hl expression, VEGFR-3 positive vessels and clinicopathological factors, especially, lymphatic metastases in oral squamous cancer;third, the dependability of VEGF-C expression and VEGFR-3 positive vessels.Materials and Methods:Llmmunohistochemical staining for VEGF-C, VEGFR-3 and nm23-Hl were performed in oral squamous cell carcinoma, precancerous change and benign lesion.2.The VEGFR-3 positive vessels were assessed through max-vessels density counting method.3.The correlation was investigated by statistical analysis, between VEGF-C, nm23-Hl expression, VEGFR-3 positive vessels and clinicopathological factors, especially, lymphatic metastases.Results:l.Oral carcinomas exhibited intense VEGF-C immunoreactivity and no or poor expression of nm23-Hl in the cytoplasm of many cancer cells, respectively. In contrast, VEGFR-3 was mainly expressed on the lymphatic endothelial cells in stroma. Precancerous and benign lesion exhibited no or faint cytoplasmic staining of VEGF-C and intense staining of nm23-Hl. Compared with benign and precancerous change, VEGF-C, VEGFR-3 and nm23-Hl expressions were significantly differences in oral squamous cancer(p<0.05).2. VEGF-C, VEGFR-3 and nm23-Hl were evaluated by immunohistochemistryand the expressions were compared with that of well-known prognostic indicators, such as age, sexuality, site, tumor stage and grade, lymph node involvement. The tissue expressions of VEGF-C was correlated significantly with clinical stage and lymphatic metastasis(p<0.05);VEGFR-3 was significantly correlated with lymph node involvement(p<0.05),but no other clinicopathological variable, and nm23-Hl was obviously related with clinical stage, histological grade and lymphatic metastasis(p<0.05). VEGFR-3 positive Vessels count was significantly higher in the VEGF-C positive tumors than in the negative tumors (p<0.05) in oral squamous cancer.ConclusionThe present study suggests that the chief role of increased expressions of VEGF-C and VEGFR-3 was to enhance lymphangiogenesis and provide a main pathway for cancer cells to disseminate, moreover, inactivation of nm23-Hl also plays an important role in lymphatic metastasis. VEGF-C, VEGFR-3 and nm23-Hl expression are valuable predictive factor of lymph node metastasis in oral cancer patients.