VEGF and VEGF type C play an important role in angiogenesis and lymphangiogenesis in human malignant mesothelioma tumours

The vascular endothelial growth factor (VEGF) family is a novel regulator o f endothelial cell proliferation. We assessed the mRNA expression of VEGF, VEGF type C (VEGF-C) and their receptors together with the microvessel dens ity (VD) and microlymphatic vessel density (LVD) in pursuit of their connec tion and prognostic value in malignant pleural mesothelioma (MPM). We used four human MPM cell lines, 54 MPM tumours and five normal pleural tissues, Expression levels for receptors and ligands were assessed by semiquantitati ve reverse transcriptase polymerase chain reaction analysis. Microvessels w ere highlighted by immunohistochemical staining for factor VIII, The discri mination of lymphatics was performed by enzyme-histochemistry for 5'-nucleo tidase after adequate inhibition of non-specific activity. The expression l evels of VEGF, VEGF-C and VEGFRs were high in all MPM cell lines. The perce ntages of tumours with higher expression compared to the mean values of nor mal pleural tissues were 31.5% (17/54) for VEGF, 66.7% (36/54) for VEGF-C, 20.4% (11/54) for fms-like tyrosine kinase (flt)-1, 42.6% (23/54) for kinas e insert domain-containing recepter (KDR) and 59.3% (32/54) for flt-4. Sign ificant positive correlations were found between VEGF-C and flt-4, VEGF and KDR, VEGF and flt-1 in tumour tissues. The association between LVD and VEG F-C expression level was especially strong (P < 0.0001, r = 0.63). There we re also significant correlations between LVD and flt-4, and VD and VEGF, No correlation, however, was found between LVD and nodal metastasis. VD was a negative prognostic indicator in this study, The associations between VEGF /VEGF-C and vessel density suggest that these factors play an important rol e in angiogenesis and lymphangiogenesis in this tumour, and assessment of v ascularity may be a useful prognostic indicator for MPM patients.