Expression Level, and Prognostic Impact of Vascular Endothelial Growth Factor (VEGF) in Non-Hodgkin Lymphoma (NHL).
Authors: Li Yiqing , Yin Songmei , Yin Linlin , Xie Shuangfeng , Nie Danian , Wang Xiuju , Ma Liping 
Published: November 2019

Abstract
Vascular endothelial growth factor (VEGF), which induces angiogenesis and increases vascular permeability, is a major growth factor mediating tumor progression. In this study, we employed immunohistochemical-staining method to detect the expression of VEGF in lymph nodes taken from39 non-Hodgkin’s lymphomas patients and analyzed the relation of the expression levels to malignant aggressiveness, treatment response, histological grade, clinical stage and prognosis. The patients had been observed for at least 5 years or until death. 9 patients with benign lymphadenopathy were acted as control. The expression of VEGF was assessed according to the percentage of immunoreactive cells in a total of 1000 neoplastic cells (quantitative analysis). Immunoreactivity was graded positive, more than 10% of carcinoma cells stained and negative, no detectable staining or less than 10% of carcinoma cells stained. Furthermore, the qualitative intensity of staining for VEGF was assessed using a scale of 0–3+. The expression analysis of VEGF revealed that in 31 out of 39 (79.49%) specimens VEGF staining was positive. The VEGF staining was always cell membrane. Significant associations were found between the expression of VEGF and histological grade, Ann Arbor stage, prognosis (according to International Prognostic Index, IPI) and chemotherapy response. Among 8 cases of low grade, 7 had lower-level expression and 1 had higher-level expression, but among 31 cases of intermediate and high grade, 13 had lower-level expression and18 had higher-level expression (P=0.044<0.05). Among 22 cases of stageI+II, 18 had lower-level expression and 4 had higher-level expression. Among 17 cases of stageIII+ IV, 2 had lower-level expression and 15 had higher-level expression (P=0.000<0.05). Among 13 cases of lower-level expression, 12 (92.3%) were in complete remission (CR) and 1 was in non remission (NR). Among 13 cases of higher-level expression, 6 (46.2%) were in CR or partial remisson (PR) and 7 were in NR (P=0.030<0.05). Among 27 cases of low-risk and low-intermediate-risk, 17 had lower-level expression and 10 had higher-level expression (P=0.014<0.05). We also found high VEGF was associated with a high serum lactate dehydrogenase (LDH) level. Among 20 cases with normal LDH level, 13 had lower-level expression and 7 had higher-level expression. Among 14 cases with higher-level LDH; 3 had lower-level expression and 11 had higher-level expression (P=0.017<0.05). Of 39 patients, 35 patients were followed up. In the lower-level expression group, 5-year survival rate was 91.67%. 5-year survival rate of higher-level expression group was 41.89%. There’s statistical difference in 3-year survival rate between these two groups(P=0.032<0.05). However, the expression of VEGF was not associated with age, gender, B symptoms, immunophenotyping andβ2-MG. In a conclusion, the expression of VEGF in NHL was increased. It was correlated with histopathological grade, Ann Arbor stage, chemotheraphy response and IPI It suggested that VEGF play an important role in the pathogenesis and progression of NHL and be an unfavorable prognostic factor in NHL.