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

• Published in: Cancer 2007-09, Vol.110 (6), p.1287-1294
• Main Authors: Miyahara, Mayumi, Tanuma, Jun‐ichi, Sugihara, Kazumasa, Semba, Ichiro
• Format: Article
• Language: English
• Subjects: Aged; angiogenesis; Biological and medical sciences; Biomarkers, Tumor - analysis; Biomarkers, Tumor - metabolism; Carcinoma, Squamous Cell - blood supply; Carcinoma, Squamous Cell - metabolism; Carcinoma, Squamous Cell - pathology; Female; Gene Expression Regulation, Neoplastic; Hematologic and hematopoietic diseases; Humans; Immunohistochemistry; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; lymph node metastasis; Lymphangiogenesis; Lymphatic Metastasis; Lymphatic Vessels - pathology; Male; Medical sciences; Microcirculation; Middle Aged; Mouth Neoplasms - blood supply; Mouth Neoplasms - metabolism; Mouth Neoplasms - pathology; Neovascularization, Pathologic - metabolism; oral squamous cell carcinoma; Predictive Value of Tests; Prognosis; Survival Analysis; Time Factors; Tumors; Up-Regulation; Vascular Endothelial Growth Factor C - analysis; Vascular Endothelial Growth Factor C - metabolism
• ISSN: 0008-543X; 1097-0142
• DOI: 10.1002/cncr.22900

BACKGROUND. 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. METHODS. 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. RESULTS. 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). CONCLUSIONS. 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. Cancer 2007. © 2007 American Cancer Society. The results from this study suggested that lymphangiogenesis predominantly influences metastasis‐free survival in patients with oral squamous cell carcinoma (OSCC). Lymphatic vessel density was a more useful tool than microvessel density or vascular endothelial growth factor C expression for deciding on therapeutic strategies in patients with OSCC.