The prognostic significance of VEGF-C and VEGF-A in non-Hodgkin lymphomas

Angiogenesis and lymphangiogensis are important in the proliferation and survival of the malignant hemeopoietic neoplasms. The aim of this study is to determine the prognostic role of angiogenesis and lymphangiogenesis in the development of lymphoma. For this aim, VEGF-A and VEGF-C were explored by immunohistochemistry in 177 cases. VEGF-C and VEGF-A were found to be positive in 34 and 61% of the samples. There was a good correlation between VEGF-C and VEGF-A expression (p=0.0001). The clinical prognostic indicators were not significantly different between VEGF-C (+) and (-) and/or VEGF-A (+) and (-) cases. Overall survival (OS) rate was shorter in cases with VEGF-A (+) and VEGF-C (+) cases than with negative cases (p=0.03 and p=0.0005, respectively). The OS was significantly shorter in aggressive lymphomas expressing VEGF-A and VEGF-C but not in indolent lymphomas. The results of Cox regression analyses showed that VEGF-A and VEGF-C expressions are independent prognostic parameters (OR: 2.6, 95% CI: 1.3-5.0 for both (+) cases). In conclusion, VEGF-C and VEGF-A were positive in 34 and 61%, respectively, of the cases with NHL. The significant correlation between VEGF-C and VEGF-A suggests that lymphangiogenesis is important in the pathogenesis of lymphomas as shown in angiogenesis. The significantly shorter survival rates of VEGF-C and/or VEGF-A expressions indicate that angiogenesis and lymphangiogenesis are important in clinical outcome. Autocrine VEGF-A and VEGF-C crostalks in lymphoma cells are important in lymphoma biology and inhibition of these signals with anti-angiogenic/anti-lymphangiogenic drugs and combination with chemo-immunotherapy regimens will be more useful in these cases.