Abstract
Background Oral squamous cell carcinoma (OSCC) is the most common oral malignancy that preferentially spreads to the cervical lymph node which, when involved, complicates the anticancer therapy and threatens the patient life. It was suggested that lymph node metastasis may be facilitated by lymphangiogenesis. VEGF-C is one of the most important lymphangiogenic inducers that promotes the lymphatic vessels growth and supports the survival of adult lymphatic endothelial cells. Methods Lymphatic vessels density (LVD) and LV morphometry were digitally evaluated using D2-40. The expression of VEGF-C was also assessed using immunohistochemistry and real-time polymerase chain reaction in 6 normal oral mucosa cases and 72 cases of OSCC. The correlation between LVD and LV morphometry, VEGF-C, and lymph node metastasis was statistically assessed. Results A positive cytoplasmic expression of VEGF-C was detected in both epithelial and connective tissue cells in 97% of OSCC, while all normal tissues reacted negatively. A greater expression of VEGF-C was associated with larger and more dilated LV and lymph node metastasis but not with LVD. Conclusion VEGF-C is actively involved in the invasion and metastasis of OSCC via inducing morphological changes in LV. VEGF-C may be a promising target for anticancer therapy.
Highlights
Oral cancer has occupied the sixth position in the cancer incidence ranking worldwide [1, 2] with Oral squamous cell carcinoma (OSCC) representing 80–90% of all oral malignancies [3, 4]
The positive immunoreaction of vascular endothelial growth factor C (VEGF-C) was detected as a brownish color in surface epithelium, in the invading epithelial masses and in the tumor-associated stromal cells including fibroblasts and endothelial and inflammatory cells
We investigated OSCC for the expression of VEGF-C at the gene and protein levels, in an attempt to examine the relation of such expression to the tumor lymphangiogenic activity, as a promoter mechanism for tumor progression
Summary
Oral cancer has occupied the sixth position in the cancer incidence ranking worldwide [1, 2] with OSCC representing 80–90% of all oral malignancies [3, 4]. Despite advances in anticancer therapy, the prognosis remains unfavorable and 50% of patients die from this disease. This is due to lack of effective diagnostic and prognostic methods which can guide and optimize appropriate treatment strategies at early stages [5]. Oral squamous cell carcinoma (OSCC) is the most common oral malignancy that preferentially spreads to the cervical lymph node which, when involved, complicates the anticancer therapy and threatens the patient life. The correlation between LVD and LV morphometry, VEGF-C, and lymph node metastasis was statistically assessed. A greater expression of VEGF-C was associated with larger and more dilated LV and lymph node metastasis but not with LVD. VEGF-C may be a promising target for anticancer therapy
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