Soluble VEGFR‐2 Expression in Head and Neck Malignant Tumors

Abstract

Objective: 1) Define the spatial pattern of expression of soluble vascular endothelial growth factor receptor 2 (sVEGFR-2), a recently discovered receptor that has an important role in tumor lymphangiogenesis, in head and neck malignant tumors. 2) Examine the relationship between sVEGFR-2 expression and lymphatic vessel density in head and neck malignant tumors. Method: One hundred ten paraffin-embedded tissue samples from patients with malignant tumors were stained using immunohistochemistry for sVEGFR-2 and podoplanin, a marker for lymphatic vessels. Tissues studied included: squamous cell carcinoma of the larynx (61), oral cavity (16), oropharynx (20), hypopharynx (5), nasopharynx (1). Papillary (4), medullary (2), and follicular (1) thyroid cancers were also examined. Results: sVEGFR-2 expression was identified in all squamous cell carcinomas of the head and neck. Expression was specific to the endothelial cells in blood vessels of both malignant tissue as well as adjacent normal tissues. sVEGFR-2 was not expressed in lymphatic vessels. This secreted protein was also expressed in tissue stroma. Decreased expression of sVEGFR-2 was correlated with increased lymphatic vessel density in tumors, as measured by podoplanin expression. sVEGFR-2 was minimally expressed in normal thyroid tissue but was abundant in the basement membrane of papillary thyroid cancer cells. Conclusion: We have provided the first evidence of sVEGFR-2 expression in head and neck malignant tumors. Its expression correlates with lymphatic vessel density in head and neck malignant tumors and ongoing studies will reveal the precise function of sVEGFR-2 in nodal metastasis and disease progression.