Tumor lymphangiogenesis correlates with lymph node metastasis and clinicopathologic parameters in oral squamous cell carcinoma.
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.
Department of Maxillofacial Diagnostic and Surgical Science, Field of Oral and Maxillofacial Rehabilitation, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
Mayumi
M
Miyahara
Jun-Ichi
J
Tanuma
Kazumasa
K
Sugihara
Ichiro
I
Semba
D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000098:blood supply / Q000378:metabolism / Q000473:pathology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D042583:Lymphangiogenesis; D008207:Lymphatic Metastasis; D042601:Lymphatic Vessels / Q000473:pathology*; D008297:Male; D008833:Microcirculation; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000098:blood supply / Q000378:metabolism / Q000473:pathology*; D009389:Neovascularization, Pathologic / Q000378:metabolism*; D011237:Predictive Value of Tests; D011379:Prognosis; D016019:Survival Analysis; D013997:Time Factors; D015854:Up-Regulation; D042582:Vascular Endothelial Growth Factor C / Q000032:analysis / Q000378:metabolism*
D014408:Biomarkers, Tumor; D042582:Vascular Endothelial Growth Factor C