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

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, ß2 microglobulin (ß2M) 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.

Vascular endothelial growth factor-A and -C: expression and correlations with lymphatic metastasis and prognosis in colorectal cancer.

Previous studies obtained contradicting results regarding the correlation between expression of VEGF-A, VEGF-C and colorectal cancer patients' clinicopathological features and prognosis. Moreover, the association between the growth factors' expression and lymphatic vessel invasion (LVI) with intratumoral and peritumoral difference has not been reported. In this study, 81 primary colorectal cancer samples were immunohistochemically stained for VEGF-A, VEGF-C and podoplanin. The expression of VEGF-A and VEGF-C in marginal portion was significantly higher than those in central portion (P = 0.000 for both). The expression of VEGF-A in marginal portion was correlated with lymph node metastasis (P = 0.031). The expression of VEGF-C in marginal portion was correlated with TNM stage (P = 0.045), peritumoral LVI (P = 0.048) and lymph node metastasis (P = 0.019). The group with high VEGF-A expression in marginal portion showed worse survival than the low expression group (P = 0.039). Patients with high expression of VEGF-C in the marginal portion were not significantly different from those with low VEGF-C expression (P = 0.121). Patients with high expression of both VEGF-A and VEGF-C in the marginal portion showed the worst survival (P = 0.015). In conclusion, increased expression of VEGF-A and VEGF-C in marginal portion of colorectal cancer was correlated with lymph node metastasis. VEGF-C facilitates colorectal cancer cells invade into peritumoral lymphatic vessels, and different mechanisms may exist in the invasion of tumor cells into peritumoral and intratumoral lymphatic vessels. Assessment the expression of both VEGF-A and VEGF-C in the marginal portion of tumor may help to identify patients with colorectal cancer with unfavourable overall survival.

Intratumoral as well as peritumoral lymphatic vessel invasion correlates with lymph node metastasis and unfavourable outcome in colorectal cancer.

The aim of this study was to assess the intratumoral and peritumoral distribution of lymphatic vessel density (LVD) and lymphatic vessel invasion (LVI) in colorectal cancer and their relationships with patients' clinicopathological characteristics and survival. Paraffin sections of 81 primary colorectal cancers were examined by immunohistochemical staining using monoclonal antibody D2-40. Peritumoral LVD was significantly higher than intratumoral LVD (P = 0.000). Both intratumoral LVD and peritumoral LVD were correlated with the presence of LVI (P = 0.006 and P = 0.003, respectively). LVI, intratumoral LVI and peritumoral LVI were identified, respectively in 38, 28 and 32% of the samples investigated. Both intratumoral LVI and peritumoral LVI were correlated with lymph node metastasis (P = 0.030 and P = 0.014, respectively). Lymph node metastasis, the presence of intratumoral LVI and peritumoral LVI were adversely associated with the 5-year overall survival in a univariate analysis (P = 0.001, P = 0.011 and P = 0.017, respectively). Multivariate analysis using Cox proportional hazard model showed that neither intratumoral LVI nor peritumoral LVI was an independent prognostic factor of overall survival. The results of this study demonstrated that intratumoral as well as peritumoral LVI was associated with lymph node metastasis and adverse outcome in colorectal cancer.