Microvessel density (MVD) and vascular endothelial growth factor expression (VEGF) in human oral squamous cell carcinoma.

Carcinogenesis is thought to be dependent on neovascularization. Vascular endothelial growth factor (VEGF) is a glycoprotein that has the capability of increasing vascular proliferation and permeability. VEGF has been found to be expressed in several different types of tumours and it may contribute to the progression of malignant tumours. Increased microvessel density (MVD) has been described in oral squamous cell carcinoma (OSCC) and seems to be related to patient prognosis. Fifty-two cases of OSCC were evaluated in the present study. Immunostaining for VEGF and Factor-VIII was performed. The MVD was evaluated in G1, G2 and G3 tumours. The differences between these 3 groups were statistically significant (p = 0.0331). MVD was also evaluated in lymph-node negative and lymph-node positive cases: the differences between these two groups were statistically significant (p < 0.0001). VEGF expression was evaluated in G1, G2 and G3 tumours. The differences between the 3 groups were not statistically significant (p = 0.289), even if an increasing trend in the VEGF positivity was evident from G1 to G3. The difference of VEGF expression between tumours with and without lymph node metastases was not significant (p = 0.196). No correlation was present between intensity of VEGF positivity and histological grading or lymph-node status and between VEGF and MVD. Our data showed that MVD was correlated with grading and lymph-node status, while no similar correlation was found for VEGF.

Artese L ，Rubini C ，Ferrero G ，Fioroni M ，Santinelli A ，Piattelli A ... -  《ANTICANCER RESEARCH》

Expression of vascular endothelial growth factor (VEGF) and its receptors (Flt-1 and Flk-1) in esophageal squamous cell carcinoma.

Kato H ，Yoshikawa M ，Miyazaki T ，Nakajima M ，Fukai Y ，Masuda N ，Fukuchi M ，Manda R ，Tsukada K ，Kuwano H ... -  《ANTICANCER RESEARCH》

Expression of endothelial nitric oxide synthase and vascular endothelial growth factor in oral squamous cell carcinoma: its correlation with angiogenesis and disease progression.

Angiogenesis is a crucial step in the successful growth, invasion, and metastasis of a tumor. It has been popularly accepted that vascular endothelial growth factor (VEGF) is the most potent angiogenic factor in tumor angiogenesis. As another possible star molecule responsible for tumor angiogenesis, the role of nitric oxide (NO) in tumor biology has gained much attention in recent years. The aim of this study was to investigate whether the expression of endothelial nitric oxide synthase (eNOS) and VEGF in oral squamous cell carcinoma (OSCC) is associated with angiogenesis. The present study also made a preliminary exploration of the possible cross-talking existing between eNOS and VEGF during tumor angiogenesis. In this study, expression of eNOS and VEGF were studied immunohistochemically in tissue sections from 40 patients with OSCC and 20 normal controls. To exclude eNOS antibody cross-reactivity with inducible or neuronal nitric oxide (iNOS or nNOS), eNOS expression was confirmed by using an eNOS mRNA in situ hybridization kit. The intratumoral microvessels were highlighted by immunostaining with anti-factor VIII-related antigen monoclonal antibody and counted as well-established methods. Then, chi-square test or Student's t-test was performed to study the correlations between the expression of eNOS and VEGF, microvessel density (MVD), and various clinicopathologic factors. Both eNOS and VEGF expression significantly increased in OSCC tissues, with a positive rate of 47.5% and 50%, respectively. The average MVD in OSCC tissues was 23.45 per high-power field (HPF), showing an obvious association with lymph node metastasis and clinical stages of patients with OSCC. Either eNOS or VEGF positivity was correlated with vessel involvement and OSCC progression. The mean MVD was significantly higher in eNOS- or VEGF-positive tumors than in eNOS- or VEGF-negative tumors. An obvious, correlation was also seen between eNOS and VEGF expression in OSCC tissues in this study. Overexpression of eNOS and VEGF might make an important contribution to the tumor angiogenesis in OSCC. NO generation by eNOS might be implicated in the VEGF-associated angiogenic process. Further investigation of the possible cross-talking between eNOS and VEGF with respect to tumor angiogenesis is necessary.

Shang ZJ ，Li JR 《JOURNAL OF ORAL PATHOLOGY & MEDICINE》

Vascular endothelial growth factor expression predicts outcome and lymph node metastasis in squamous cell carcinoma of the esophagus.

Shih CH ，Ozawa S ，Ando N ，Ueda M ，Kitajima M ... -  《CLINICAL CANCER RESEARCH》

Tumor lymphangiogenesis correlates with lymph node metastasis and clinicopathologic parameters in oral squamous cell carcinoma.

Lymphatic vessel density (LVD) and microvessel density (MVD) are important parameters for assessing the malignant potential of tumors and patient survival. In this report, the authors defined LVD as the density of D2-40-positive lymphatic vessels and MVD as the density of CD105-positive microvessels per unit area of tissue. It was reported previously that vascular endothelial growth factor C (VEGF-C) is a major modulator of LVD and MVD. The objectives of this study were to clarify the clinical and prognostic significance of both LVD and MVD in oral squamous cell carcinoma (OSCC) and to elucidate the lymphangiogenic and angiogenic activities of VEGF-C in cancer tissues. In total, 110 OSCC tissue samples were evaluated for LVD, MVD, and expression of VEGF-C using immunohistochemistry. Correlations among these parameters and clinicopathologic factors were examined. LVD was significantly higher in tumors that had very high expression of VEGF-C compared with tumors that had no/weak expression of VEGF-C. LVD correlated well with lymph node metastasis (P < .001). MVD was correlated significantly with positive lymph node metastasis (P < .001) but not with VEGF-C expression. In contrast, high expression of VEGF-C was correlated significantly with advanced tumor status (P = .041). Survival rates were lower in patients who had higher LVD (P < .001), higher MVD (P = .0028), and strong VEGF-C expression (P = .048). Lymphangiogenesis predominantly influenced metastasis-free survival. The current results suggested that LVD is a more useful tool than MVD and VEGF-C for deciding on therapeutic strategies in patients with OSCC.

Miyahara M ，Tanuma J ，Sugihara K ，Semba I ... -  《CANCER》