Lymphangiogenesis in non-Hodgkin’s lymphoma and its correlation with cyclooxygenase-2 and vascular endothelial growth factor-C

Abstract

Abstract. We aimed to investigate the correlations between lymphangiogenesis, cyclooxygenase (COX)-2 and vascular endothelial growth factor-C (VEGF-C) in non-Hodgkin's lymphoma (NHL) and their associations with the clinical parameters of patients. A total of 75 patients diagnosed with NHL were enrolled in this study. Of the 75 patients, 14 (18.7%) had low-grade and 61 (81.3%) had aggressive lymphoma. We examined the immunohistochemical expression of COX-2 and VEGF-C and estimated lymphangiogenesis by counting lymphatic vessels expressing lymph vessel endothelial hyaluronan receptor-1 (LYVE-1). Our results showed that lymphatic vessel density (LVD) was positive in 59.0% of the cases with aggressive morphology, while the LVD positive rate of indolent lymphoma was only 28.6% (P=0.039). Both COX-2 and VEGF-C were correlated with lymphangiogenesis (P=0.030 and 0.000, respectively). The expression levels of COX-2 and VEGF-C were significantly correlated (P= 0.015). LVD, COX-2 and VEGF-C were not correlated with the gender, age, lactate dehydrogenase (LDH) levels, β2 microglobulin (β2M) levels, extranodal involvement, disease stage, B symptoms or international prognostic index of the patients. In conclusion, lymphangiogenesis was correlated with aggressive histology in NHL. COX-2 and VEGF-C are inducers of lymphangiogenesis and their expression levels were correlated in NHL.

Cyclooxygenase-2 immunoexpression in intestinal epithelium and lamina propria of cats with inflammatory bowel disease and low grade alimentary lymphoma

“…No correlations were observed between FCEAI, histological alterations, IBD and LGAL with COX-2 expression. Similar results have been obtained in canine IBD, and human lymphoma and IBD [ 44 , 46 , 58 – 60 ].…”

“…However, other studies in canine lymphoma did not find COX-2 immunoreactivity [ 53 , 56 ]. Furthermore, studies in humans revealed that most of non-Hodgkin’s lymphoma (> 50% of cases) had COX-2 expression by tumour cells [ 58 – 60 ]. Thus, COX-2 upregulation in lymphomas has been associated with the aggressiveness, relapsed, worst response to therapy and less overall survival [ 58 – 61 ].…”

Podoplanin Expression Correlates with Disease Progression in Mycosis Fungoides

“…Considering haematological malignancies, positive correlation between increased number of PDPN-positive vessels and disease progression was reported in Sézary syndrome, the most common, aggressive CTCL (33). Increased LVD was also associated with aggressive histology in non-Hodgkin's lymphomas (NHL) (23).…”

“…In breast, prostate and colon cancer increased expression of VEGF-C correlated with high lymphatic vessel density (LVD) and poor survival (16)(17)(18)(19)(20)(21). In haematological malignancies, increased lymphangio genesis was found to be correlated with aggressiveness and poor clinical outcome of lymphoma (22,23).…”

Expression of SOX18 in Mycosis Fungoides

“…It is also one of the key markers of disease outcome. Numerous studies published over the past decades showed a close relationship between the vascularization of the tumour, its histological grade and clinical progression and poor prognosis in non-Hodgkin's lymphomas (NHL) (25)(26)(27)(28). In contrast, relatively little attention was paid to primary CTCLs in the aspect of angio-and lymphangiogenesis.…”