INTRODUCTION: Activation of angiogenesis stimulated by Vascular endothelial growth factor (VEGF) in host cells play a role in response to damaged gastric mucosal in gastritis patient with Helicobacter pylori (H. pylori) infection. The study showed that presence of polymorphisms in VEGF gene is associated with an increased risk of several disorders like gastric cancer. Infiltration of neutrophils in the gastric mucosa characterized acute gastritis. It can become chronic inflammation characterized by lymphocyte infiltration. This condition will complicate glandular atrophy and intestinal metaplasia in the gastric mucosal epithelium and subsequently cause gastric malignancy. The aim of this study to analyze association between VEGF +936 C>T polymorphism gene with degree of neutrophils and lymphocytes infiltration in gastritis patients with H. pylori. METHODS: Samples were obtained through consecutive sampling in April-August 2019. Gastritis was ensured by endoscopy while histological feature was defined by Sydney system. H. pylori was examined by Campylobacter Like Organism test (CLO) and VEGF + 936 C> T gene polymorphism was ensured using PCR TaqMan SNP Genotyping Assay rs2010963. Chi-square analysis was used in this study to determine the association between VEGF + 936 C>T gene polymorphism with degree of neutrophils and lymphocytes infiltration. RESULTS: Of 60 gastritis patients, there were CT genotype (37.5%), followed by CC genotypes (36.7%), and TT genotypes (35%). Patients with CC genotype increased the risk of 18 times moderate and severe neutrophil infiltration compared to CT+TT genotypes (p=0.001). There was no relationship between VEGF + 936 C>T polymorphism and the degree of lymphocytes infiltration (p=0.293) CONCLUSION: There was a significant association between VEGF + 936 C>T polymorphism and the degree of neutrophil infiltration but there was no association between VEGF + 936 C>T polymorphism and the degree of neutrophil infiltration.
Vascular Endothelial Growth Factor C ; Vascular Endothelial Growth Factor A ; Gastritis ; Polymorphism, Genetic

PURPOSE: Animal models show a strong relationship between lymphangiogenesis and lymph node metastasis. However, the clinical significance of lymphangiogenesis in patients with colorectal cancer (CRC) remains uncertain. This study aimed to evaluate the association between c-Met and lymphangiogenic factors and to elucidate the prognostic significance of c-Met in patients with CRC. METHODS: A total of 379 tissue samples were obtained from surgically resected specimens from patients with CRC at Soonchunhyang University Cheonan Hospital between January 2002 and December 2010. The expressions of c-Met, vascular endothelial growth factor (VEGF)-C, VEGF-D, VEGF receptor (VEGFR)-3, and podoplanin were examined using immunohistochemistry. The expression of c-Met and clinical factors were analyzed. RESULTS: Of the 379 tissues, 301 (79.4%) had c-Met expression. High expression of c-Met in tumor cells was significantly associated with high expression of VEGF-C (P < 0.001) and VEGFR-3 (P = 0.001). However, no statistically significant association with podoplanin (P = 0.587) or VEGF-D (P = 0.096) was found. Of the 103 evaluable patients, expression of c-Met in tumor cells was significantly associated with advanced clinical stage (P = 0.020), positive lymph node status (P = 0.038), and high expression of VEGF-C (P = 0.020). However, no statistically significant association with podoplanin (P = 0.518), VEGFR-3 (P = 0.085), VEGF-D (P = 0.203), or overall survival (P = 0.360) was found. CONCLUSION: Our results provide indirect evidence for an association and possible regulatory link of c-Met with the lymphangiogenic markers, but c-Met expression in patients with CRC is not a prognostic indicator for overall survival.
Chungcheongnam-do ; Colorectal Neoplasms* ; Humans ; Immunohistochemistry ; Lymph Nodes ; Lymphangiogenesis ; Models, Animal ; Neoplasm Metastasis ; Receptors, Vascular Endothelial Growth Factor ; Vascular Endothelial Growth Factor A ; Vascular Endothelial Growth Factor C ; Vascular Endothelial Growth Factor D ; Vascular Endothelial Growth Factor Receptor-3

PURPOSE: The aim of this study is to explore signal transducer and activator of transcription 3 (STAT3) expression in breast cancer and to analyze the detailed mechanism that STAT3 contributes to the progression of breast cancer. METHODS: We retrospectively analyzed the clinicopathologic characteristics and overall survival (OS) of 140 breast cancer patients after curative surgery, and detected STAT3 expression, phosphorylated STAT3 (pSTAT3) expression, Ki-67 expression, vascular endothelial growth factor (VEGF)-C and -D expression in breast cancer tissues, and adjacent nontumor tissues. Survival analysis and relationship analysis were adopted for demonstrated the important mechanism of STAT3 contribution to progression of breast cancer. RESULTS: STAT3 expression, pSTAT3 expression, Ki-67 expression, VEGF-C expression, and VEGF-D expression in breast cancer tissues were significantly higher than those in adjacent nontumor tissues, respectively. With survival analysis, only number of lymph node metastasis (N stage) was identified as the independent predictors of the OS of breast cancer patients. Besides, we demonstrated there was the most prominent correlation between STAT3 expression and lymph node metastasis in breast cancer tissues by using the multinominal regression method. CONCLUSION: STAT3, a poor survival biomarker potential association with lymph node metastasis, was suitable for predication the OS of breast cancer patients after curative resection.
Breast ; Breast Neoplasms ; Humans ; Lymph Nodes ; Neoplasm Metastasis ; Prognosis ; Retrospective Studies ; STAT3 Transcription Factor ; Vascular Endothelial Growth Factor A ; Vascular Endothelial Growth Factor C ; Vascular Endothelial Growth Factor D

PURPOSE: We aimed to investigate the correlations between expressions of angiogenic cytokines VEGF-A, C, D of primary colorectal cancer and liver metastasis. METHODS: We examined paraffin-embedded primary colorectal cancer tissue from 45 patients who had liver resection due to colorectal liver metastasis (metastasis group) and 37 patients who had surgical resection due to colorectal cancer only (control group). In the control group, local recurrence and distant metastasis had not occurred. Immunohistochemical staining for VEGF-A, C and D was performed. We analysed the correlations between expression of VEGF-A, C and D in primary colorectal cancer tissues and clinicopathologic parameters. RESULTS: VEGF-A expressions of primary colorectal carcinoma were not different between the two groups. VEGF-C was more frequently expressed in the metastasis group (P=0.008) but VEGF-D was more expressed in the control group (P=0.003). Patients with VEGF-C negative and VEGF-D positive expression were predominant in the control group (P=0.020). Tumor location, T stage, lymph node metastasis and tumor differentiation were not related with the expressions of VEGF-A, C, D but only preoperative CEA was positively correlated with VEGF-A and C expression. CONCLUSION: Expressions of VEGF-C in primary tumor were more frequent in metastatic colorectal cancer and expressions of VEGF-D were more frequent in nonmetastatic colorectal cancer. More large-scale prospective studies for VEGF-C and D expression in colorectal cancer are necessary.
Colorectal Neoplasms ; Cytokines ; Humans ; Liver ; Lymph Nodes ; Neoplasm Metastasis ; Recurrence ; Vascular Endothelial Growth Factor A ; Vascular Endothelial Growth Factor C ; Vascular Endothelial Growth Factor D

OBJECTIVE: Vascular endothelial growth factor(VEGF)-C is involved in lymphangiogenesis and spreading of cancer cells via lymphatic vessels. The aim of the present study is to investigate the relationship between the absence of cerebral lymphatic vessels and low metastatic rate of brain tumors. METHODS: Immunohistochemical stains were performed for VEGF-C and VEGF in surgically resected specimens from 57 patients with primary(38 cases, low grade : 10 cases, high grade : 28 cases) and metastatic(19 cases) brain tumor. RESULTS: The expression of VEGF-C was higher in metastatic carcinoma(68%) than in high-grade primary tumor(29%). There was no difference for VEGF expression between high grade brain tumor (71%) and metastatic carcinoma(58%). CONCLUSION: Low VEGF-C expression of primary brain tumors may play a role in low metastatic rate of brain tumors.
Brain Neoplasms* ; Brain* ; Coloring Agents ; Humans ; Lymphangiogenesis ; Lymphatic Vessels ; Vascular Endothelial Growth Factor A ; Vascular Endothelial Growth Factor C*

PURPOSE: Although the vascular endothelial growth factor (VEGF) superfamily has been identified to critically influence tumor-related angiogenesis, the prognostic significance of a VEGF expression in gastric cancer is still controversial. Accordingly, the present study analyzed the VEGF-A and VEGF-C expressions and their impact on the prognosis of patients with gastric cancer. MATERIALS AND METHODS: Three hundred seventy-five consecutive patients who underwent surgical resection for gastric adenocarcinoma with a curative intent were enrolled in the present study. Immunohistochemical staining for VEGF-A and VEGF-C was performed using the formalin fixed, paraffin embedded tumor tissues. RESULTS: Positive VEGF-A and VEGF-C expressions were observed in 337 (90.1%) and 278 (74.9%) cases, respectively. The survival analysis showed that the expression of VEGF-A and VEGF-C had no effect on the OS and DFS. On the multivariate analysis that included age, gender and the TNM stage, no significant association between the grade of the VEGF-A or VEGF-C expression and survival was observed. CONCLUSION: The current study suggests that the tissue expression of VEGF-A or VEGF-C alone is not an independent prognostic marker for patients with surgically resected gastric adenocarcinoma.
Adenocarcinoma ; Formaldehyde ; Humans ; Multivariate Analysis ; Paraffin ; Prognosis ; Stomach Neoplasms ; Vascular Endothelial Growth Factor A ; Vascular Endothelial Growth Factor C

OBJECTIVETo investigate the relationship between vascular endothelial growth factor C (VEGF-C) expression, VEGFR-3 expression, lymphangiogenesis and angiogenesis in human non-small cell lung cancer (NSCLC).

METHODSSeventy-six NSCLC samples were stained for VEGF-C, VEGFR-3 and CD34 with immunohistochemical methods. Assessment of lymphatic vessel density (LVD) and microvessel density (MVD) was performed. The expressions of VEGF-C in 24 fresh NSCLC samples were determined with Western blot assay.

RESULTSOf the 76 NSCLC cases, 55 were VEGF-C positive and 40 were VEGFR-3 positive in cancer cells. A significant positive correlation was found between VEGF-C expression and VEGFR-3 expression in cancer cells (P < 0.05). VEGF-C expression was negatively associated with differentiation of tumor cells (P < 0.05). VEGF-C expression and VEGFR-3 expression were positively associated with lymph node metastasis and lymphatic invasion (P < 0.05). LVD was positively related to VEGF-C expression, lymph node metastasis, lymphatic invasion and clinical stage (P < 0.05). There was a significant correlation between LVD and MVD (R = 0.732, P < 0.05). Patients with positive VEGF-C expression had worse outcomes than those with negative VEGF-C expression (P < 0.01).

CONCLUSIONSIn NSCLC, VEGF-C and VEGFR-3 are related to the lymphangiogenesis, angiogenesis, and occurrence and development of lung cancers. VEGF-C expression could be a useful predictor of poor prognosis in NSCLC.

Carcinoma, Non-Small-Cell Lung ; metabolism ; Endothelial Growth Factors ; biosynthesis ; Humans ; Immunohistochemistry ; Lung Neoplasms ; metabolism ; Vascular Endothelial Growth Factor C ; Vascular Endothelial Growth Factor Receptor-3 ; biosynthesis

BACKGROUND: Vascular endothelial growth factor (VEGF)-C and VEGF-D are novel growth factors that regulate lymphatic vessel growth. This study was designed to examine whether the expression of three VEGF family members, VEGF-A, VEGF-C and VEGF-D are associated with the clinicopathologic parameters, especially with lymph node metastasis, in advanced gastric carcinomas. METHODS: Immunohistochemical staining was performed for VEGF-A, VEGF-C, and VEGF-D in the surgically resected specimens from 102 patients with advanced gastric carcinoma. The mRNA expressions of the three VEGF family members were assessed in 16 cases of tumor tissues and their corresponding non-neoplastic tissues. RESULTS: Of the 102 gastric carcinomas, 74 (73%), 82 (80%), and 34 (33%) cases showed cytoplasmic immunoreactivity for VEGF-A, VEGF-C and VEGF-D, respectively. Both VEGF-A and VEGF-C expressions were associated with lymphatic invasion and lymph node metastasis (p<0.05), but the VEGF-D expression was not associated with them (p>0.05). In the tumor tissue, VEGF-C mRNA expression was greater, while VEGF-D mRNA expression was lower than in the nonneoplatic tissue adjacent to the tumor. CONCLUSIONS: VEGF-A and VEGF-C may play important roles for the lymphatic spread of gastric carcinoma. We suggest that neutralizing both VEGF-A and VEGF-C may be reguired to block lymph node metastasis.
Adenocarcinoma* ; Cytoplasm ; Humans ; Intercellular Signaling Peptides and Proteins ; Lymph Nodes ; Lymphatic Vessels ; Neoplasm Metastasis ; RNA, Messenger ; Vascular Endothelial Growth Factor A* ; Vascular Endothelial Growth Factor C ; Vascular Endothelial Growth Factor D ; Vascular Endothelial Growth Factors*

The study was to investigate the expression of VEGFA, VEGFC, angiopoietin-1, angiopoietin-2 and their receptors on yolk sac blood island, AGM region during gestation of 3th-12th weeks of human embryo. Human embryo contingently aborted at 3 - 12 weeks of gestation were collected with signed agreements of the pregnant women suffered from accidental abortions. The specimens were fixed by 4% paraformaldehyde and embedded by paraffin. 5 micro m serial sections were made. HE and immunohistochemistry method (SABC) and light-microscope were employed. The results showed that VEGFA and its receptors flt1/flk-1, VEGFC and its receptor flt-4, angiopoietin-2 and its receptor tie-2 proteins were expressed strongly and angiopoietin-1 was weakly expressed by hematopoietic cells and vascular endothelial cells of blood island at 21 and 25 days of gestation. In the 4th week of gestation, immuno-positive reaction of these factors and their receptors appeared in the aorta and mesonephros deposited in larger, rounded and nucleated cells which represented hematopoietic cells. Up to 7th week, positive hematopoietic cells in the regions were much abundant. The number of positive cells decreased at 8th week. Up to 12th week, almost all blood cells were immuno-negative. VEGFA, flt-1, flt-4, angiopoietin-1, angiopoietin-2 and Tie-2 protein were expressed mainly by gonad at 6 - 8 weeks, but it did not express VEGFC and flk-1. The immuno-reaction of the factors and their receptors could not detected in vascular endothelial cells during 3-12th weeks of gestation. It is concluded that hematopoietic cells and endothelial cells in blood island of yolk sac, mesonephros and dorsal aorta co-expressed some factors and their receptors in relation to vasculogenesis and hematopoiesis. Intraembryonic hematopoiesis began in the 4th week of gestation.
Angiopoietin-1 ; analysis ; Angiopoietin-2 ; analysis ; Embryo, Mammalian ; chemistry ; Extracellular Matrix Proteins ; analysis ; Humans ; Immunohistochemistry ; Receptor, TIE-2 ; analysis ; Receptors, Vascular Endothelial Growth Factor ; analysis ; Vascular Endothelial Growth Factor A ; analysis ; Vascular Endothelial Growth Factor C ; analysis ; Vascular Endothelial Growth Factor Receptor-1 ; Vascular Endothelial Growth Factor Receptor-2 ; analysis ; Vascular Endothelial Growth Factor Receptor-3 ; analysis ; Yolk Sac ; chemistry

PURPOSE: Lymphatic spread of tumor is an important prognostic factor for patients with non-small cell lung carcinoma (NSCLC). Vascular endothelial growth factor-C (VEGF-C) and VEGF-D play important roles in lymphangiogenesis via the VEGF receptor 3 (VEGFR-3). We sought to determine whether VEGF-C, VEGF-D and VEGFR-3 are involved in the clinical outcomes of patients with resected NSCLC. MATERIALS AND METHODS: Using immunohistochemical staining, we investigated the protein expressions of VEGF-C, VEGF-D and VEGFR-3 in the tissue array specimens from patients who underwent resection for NSCLC. The immunoreactivity for p53 was also examined. The clinicopathological implications of these molecules were statistically analyzed. RESULTS: Analysis of a total of 118 specimens showed that VEGF-C, VEGF-D and their co-expression were significantly associated with more advanced regional lymph node metastasis (p=0.019, p=0.044 and p=0.026, respectively, N2 versus N0 and N1). A VEGFR-3 expression had a strong correlation with peritumoral lymphatic invasion (p=0.047). On the multivariate analysis for survival and recurrence, pathologic N2 lymph node metastasis was the only independent prognostic factor, but none of the investigated molecules showed any statistical correlation with recurrence and survival. CONCLUSIONS: The present study revealed that high expressions of VEGF-C and VEGF-D were strongly associated with more advanced regional lymph node metastasis in patients with resected NSCLC.
Carcinoma, Non-Small-Cell Lung ; Humans ; Lung ; Lymph Nodes ; Lymphangiogenesis ; Multivariate Analysis ; Neoplasm Metastasis ; Receptors, Vascular Endothelial Growth Factor ; Recurrence ; Vascular Endothelial Growth Factor A ; Vascular Endothelial Growth Factor C ; Vascular Endothelial Growth Factor D ; Vascular Endothelial Growth Factor Receptor-3 ; Vascular Endothelial Growth Factors