Expression and significance of VEGF-C and FLT-4 in gastric cancer

AIM:To investigate the expression of pathological factors of VEGF-C and its receptor FLT-4 in primary gastric cancer and adjacent normal tissues.METHODS: The expression of VEGF-C and FLT-4 was studied in 80 primary gastric cancers and adjacent normal tissues from the same patients by semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) and immu mohistochemistry.RESULTS:Both primary gastric cancer and adjacent normal tissue could express VEGF-C and FLT-4, and FLT-4 expression was also detected in endothelial cells of stromal blood vessels and lymphatic vessels. There was a significant difference in expression of VEGF-C between primary tumor and adjacent normal tissue samples (P=0.01),and a statistical correlation between VEGF-C and FLT-4 expression in tumors (P=-0.00886). With regard to VEGF-C expression,there was a significant difference between moderate-poor differential type and high differential type (P=0.032), and a significant difference between positive and negative lymph node metastases (P=0.024).However,there was no significant difference between positive and negative serosal invasions (P=0.219).CONCLUSION: VEGF-C and its receptor FLT-4 play a role in the development of gastric cancer, and the tumors with expression of VEGF-C and FLT-4 are more likely to have lymph node metastasis.

Tumor metastasis and the reciprocal regulation of heparanase gene expression by nuclear factor kappa B in human gastric carcinoma tissue

AIM: To investigate whether NF-kB is activated in human gastric carcinoma tissues and, if so, to study whether there is any correlation between NF-kB activity and heparanase expression in gastric carcinoma. METHODS: NF-kB activation was assayed by immunohistochemical staining in formalin-fixed, paraffin-embedded specimens from 45 gastric carcinoma patients. Electrophoretic mobility shift assay (EMSA) method was used for nuclear protein from these fresh tissue specimens. Heparanase gene expression was quantified using quantitative RT-PCR. RESULTS: The nuclear translocation of RelA (marker of NF-kB activation) was significantly higher in tumor cells compared to adjacent and normal epithelial cells [(41.3±3.52)% vs (0.38±0.22) %, t=10.993, P= 0.000<0.05; (41.3±3.52)% vs(0±0.31)%, t=11.484, P= 0.000<0.05]. NF-kB activation was correlated with tumor invasion-related clinicopathological features such as lymphatic invasion, pathological stage, and depth of invasion (Z= 2.148, P= 0.032<0.05; t = 8.758, P= 0.033<0.05; t = 18.531, P = 0.006<0.05). NF-KB activation was significantly correlated with expression of heparanase gene (r= 0.194, P=0.046<0.05). CONCLUSION: NF-KB RelA (p65) activation was related with increased heparanase gene expression and correlated with poor clinicopathological characteristics in gastric cancers. This suggests NF-kB as a major controller of the metastatic phenotype through its reciprocal regulation of some metastasis-related genes.

Expression and significance of angiopoietin-2 in gastric cancer

AIM: To investigate the expression and pathological factors of Angiopoietin-2 (Ang-2) in primary gastric cancers and adjacent normal tissues.METHODS: The expression of Angiopoietin-2 and VEGF were studied in 72 primary gastric cancers and adjacent normal tissues from the same patients by semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) and immumohistochemistry.RESULTS: Ang-2 was mainly expression in tumor cells.There were significantly difference between expression of Ang-2 in primary gastric cancer and in adjacent normal tissue samples (P=-0.003). It was statistically correlation between Ang-2 and VEGF expression in tumors (P=-0.0055).With regard to Ang-2 expression in tumors, there were significant difference between early stage and advanced stage (P=-0.017), and significant difference between positive vascular involvement and negative vascular involvement (P=0.032). However, there was no significant difference between moderate-poor differential type and high differential type (P=-0.908), between positive lymph node metastasis and negative lymph node metastasis (P=0.752),between positive serosal invasion and negative serosal invasion (P=-0.764). The cases with expression of Ang-2 were increasing with advanced stage and vascular involvement.CONCLUSION: The results manifested that Angiopoietin-2, coordinated with VEGF, play role in regulating tumor angiogenesis of gastric cancer.