Participation of hypoxia-inducible factor-1alpha and lymphangiogenesis in metastatic and non-metastatic lower lip squamous cell carcinoma.

This study evaluated the lymphatic density and HIF-1alpha immunoexpression in lower lip squamous cell carcinoma (LLSCC) and their correlation with clinicopathological (nodal metastasis, clinical stage, histological grade, recurrence and disease outcome) and survival parameters in 20 metastatic and 20 non-metastatic LLSCCs. Lymphatic density was established by counting microvessels (D2-40(+)) at the tumor core (intratumoral lymphatic density, ILD) and at the invasive front (peritumoral lymphatic density, PLD) and percentages of immunopositive cells for HIF-1alpha were established. No statistically significant differences in lymphatic densities in relation to clinicopathological parameters were observed (P > 0.05). All cases exhibited nuclear and cytoplasmic HIF-1alpha immunoexpression, with relatively high percentages of positivity, but this expression was not statistically different in relation to clinicopathological variables (P > 0.05). Positive correlations were observed between ILD and PLD (P = 0.002), and between nuclear HIF-1alpha immunoexpression at the tumor core and ILD (P = 0.001). The results suggest ILD and PLD are not directly related to the development of lymph node metastasis in LLSCC. The striking expression of HIF-1alpha suggests the involvement of this protein in the etiopathogenesis of LLSCCs, possibly stimulating lymphangiogenesis at the tumor core. However, this protein does not seem to exert a determining influence on the biological aggressiveness of these tumors.