Does a growing tumour volume induce lymphangiogenesis? A study of oral/oropharyngeal cancer

Objective: Tumour cell metastasis to regional lymph nodes is an early event in the spread of metastatic tumour. We postulated that an increased primary tumour volume (PTV) may modulate cervical nodal metastasis by altering lymphangiogenesis. Setting: We investigated 48 patients who had previously been diagnosed with cancer of the oral cavity and oropharynx. Methods: The tumour area was manually outlined from an axial magnetic resonance imaging series. The three-dimensional reconstruction software automatically calculated the PTV. Immunohistochemical staining was performed with vascular endothelial growth factor (VEGF)-C, VEGF-D, and D2-40 monoclonal antibodies on the paraffin-embedded tissues obtained from the primary tumour. Main Outcome Measures: The associations among the semiquantitative scores of the VEGF-C/D stained cancer cells, lymphatic vessel density (LVD), and PTV were investigated. Results: PTV had a significant relationship with LVD (p = .037) and N+ disease (p = .024). VEGF-C expression was significantly associated with lymph node metastasis (p = .018), increased LVD (p < .001), and tumour differentiation (p = .015). However, we found no significant relationship between VEGF-C expression and the PTV. Similarly, among the various clinical factors, we found that the N stage (p = .001) and LVD (p = .008) were significantly associated with VEGF-D expression. However there was no association between VEGF-D expression and the primary PTV. Conclusions: Although PTV had a significant relationship with LVD and N+ disease, we could not find any clear correlation between the expression of VEGF-C/D and the PTV.